Photoreactive ligands and uses thereof

ABSTRACT

Disclosed herein are methods for identifying proteins as targets for interaction with a small molecule ligand. Also disclosed herein are small molecule ligands and compositions for use in profiling druggable proteins.

CROSS-REFERENCE

This application is a U.S. National Phase of International ApplicationNo. PCT/US2018/014104, filed on Jan. 17, 2018, which claims the benefitof U.S. Provisional Application No. 62/447,882, filed Jan. 18, 2017,both of which are incorporated herein by reference in their entireties.

STATEMENT AS TO FEDERALLY SPONSORED RESEARCH

This invention was made with government support under grant numbersDK099810, CA132630 and 1S10OD16357 awarded by the National Institutes ofHealth. The government has certain rights in the invention.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted electronically in ASCII format and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Mar. 14, 2018, isnamed 48054-706_831_SL.txt and is 199,103 bytes in size.

BACKGROUND OF THE DISCLOSURE

Protein function assignment has been benefited from genetic methods,such as target gene disruption, RNA interference, and genome editingtechnologies, which selectively disrupt the expression of proteins innative biological systems. Chemical probes offer a complementary way toperturb proteins that have the advantages of producing graded(dose-dependent) gain- (agonism) or loss- (antagonism) of-functioneffects that are introduced acutely and reversibly in cells andorganisms. Small molecules present an alternative method to selectivelymodulate proteins and to serve as leads for the development of noveltherapeutics.

SUMMARY OF THE DISCLOSURE

Disclosed herein, in certain embodiments, is a method of identifying aprotein capable of interacting with a small molecule ligand, comprising:(a) providing a cell sample; (b) exposing the cell sample to at leastone potential small molecule ligand having a structure comprising atleast a photoreactive diazirine group and a terminal alkyne group; (c)irradiating the cell sample with UV light; (d) performing lysis on thecell sample; (e) subjecting proteins in the post lysis material tofluorophore tagging; and (f) isolating at least one fluorophore-taggedprotein.

Disclosed herein, in certain embodiments, is a method of identifying aprotein capable of interacting with a small molecule ligand, comprising:(a) providing a cell sample; (b) exposing the cell sample to the smallmolecule ligand having a structure comprising at least a photoreactivediazirine group, and a terminal alkyne group; (c) irradiating the cellsample with UV light; (d) performing lysis on the cell sample; (e)subjecting the proteins in the post lysis material to tagging; and (f)isolating the tagged proteins for analysis to identify a protein capableof interacting with the small molecule ligand.

Disclosed herein, in certain embodiments, is a method of identifying asmall molecule ligand binding site on an isolated protein, comprising:(a) providing an isolated protein; (b) exposing the protein to at leastone of potential small molecule ligands having a structure comprising atleast a photoreactive diazirine group and a terminal alkyne group; (c)irradiating the protein with UV light; (d) tagging the protein withbiotin; (e) binding the biotin-tagged protein to solid phase beads; (f)digesting the protein to provide protein fragments; and (g) analyzingthe protein fragments to determine the small molecule ligand bindingsite.

Disclosed herein, in certain embodiments, is a method of identifying asmall molecule ligand capable of interacting with a cellular protein,comprising: (a) providing a cell which expresses the cellular protein;(b) exposing the cell to a first-small molecule ligand of predeterminedaffinity for the cellular protein and a second small molecule ligand,wherein the small molecule ligand of predetermined affinity has astructure comprising at least a photoreactive diazirine group and aterminal alkyne group; (c) irradiating the cell with UV light; (d)performing lysis on the cell; (e) subjecting proteins in the post lysismaterial to tagging of the first small molecule ligand; and (f)determining the level of tagging in the presence of the second smallmolecule ligand compared to the level of tagging in the absence of thesecond small molecule ligand.

Disclosed herein, in certain embodiments, is a small molecule ligandwhich is capable of binding to a binding site on a protein, in which theprotein is selected from Tables 1-4. In some cases, the binding site isdisclosed in Tables 1-3.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of the disclosure are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present disclosure will be obtained by reference tothe following detailed description that sets forth illustrativeembodiments, in which the principles of the disclosure are utilized, andthe accompanying drawings of which:

FIG. 1A-FIG. 1H exemplify a chemical proteomic strategy for mapping offragment-protein interactions in cells. FIG. 1A represents schematicdepiction of fully functionalized fragment (FFF) probes and experimentalworkflow to identify FFF-protein interactions in cells by quantitativeMS-based proteomics. Isotopically heavy and light amino acid-labeledcells are treated with distinct FFF probes for 30 min, followed by UVlight exposure, lysis, conjugation to biotin azide by CuAAC,streptavidin enrichment of labeled proteins, tryptic digestion andsubsequent analysis of tryptic peptides. FIG. 1B exemplifies structuresof FFF probes. Shown are the ‘constant’ (containing the diazirinephotoreactive group and clickable alkyne handle) and ‘variable’(consisting of small-molecule fragments; enclosed in box) regions ofprobes. FIG. 1C exemplifies FFF probe-protein interactions in cells.HEK293T cells were treated with probes (20 μM) for 30 min, followed byphotocrosslinking and analysis as described in FIG. 1D. Asterisk markrepresentative distinct probe-protein interactions. FIG. 1E exemplifiesadditional profiles of FFF probe-protein interactions. FIG. 1Dexemplifies experimental workflow to visualize FFF probe-proteininteractions in cells by SDS-PAGE coupled with in-gel fluorescencescanning. Cells are treated with indicated FFF probe for 30 min,followed by photocrosslinking, lysis, CuAAC conjugation to a rhodamine(TAMRA)-azide tag, separation by SDS-PAGE, and visualization by in-gelfluorescence scanning. FIG. 1E exemplifies FFF probe-proteininteractions in cells. HEK293T cells were treated with FFF probes (20μM) for 30 min in situ, followed by photocrosslinking, separation ofsoluble and membrane fractions and analysis. (FIG. 1F, FIG. 1G) Fragmentprobes show concentration-dependent labeling of proteins in HEK293Tcells (FIG. 1F), with little to no further change in protein labelingwhen incubated in cells for 5 to 30 min prior to photocrosslinking (FIG.1G). FIG. 1H exemplifies HEK293T cells were treated with FFF probes (20μM) for 30 min, and the cells were then washed 1-2× with DPBS prior tophotocrosslinking. Asterisks mark proteins that show similar extents ofprobe labeling before and after cell washing.

FIG. 2A-FIG. 2T exemplify quantitative MS-based proteomic analysis offragment-protein interactions in cells. FIG. 2A exemplifies heatmapshowing relative protein enrichment values of FFF probes (200 μM) versuscontrol 1 in HEK293T cells. FIG. 2B is a representative SILAC ratio plotof proteins differentially enriched in probe-vs-probe (13 versus 3)experiments in HEK293T cells. Proteins preferentially enriched (>3-foldby either probe, depicted with dashed lines) in 13-vs-3 experiments thatwere also preferentially enriched (>2-fold) by 13 or 3 inprobe-vs-control 1 experiments are depicted. FIG. 2B also exemplifiesproteins that were strongly enriched by both probes in probe-vs-control1 experiments and proteins not enriched by either probe. FIG. 2Cexemplifies that most proteins demonstrating preferential enrichment(>3-fold) in probe-vs-probe experiments show corresponding preferentialenrichment by the same probe in probe-vs-1 experiments. Light grayportions of bars mark fractions of proteins that were strongly enrichedby both probes in probe-vs-control 1 experiments. (FIG. 2D-FIG. 2F)Heatmaps (FIG. 2D, FIG. 2E) and extracted MS1 chromatograms ofrepresentative tryptic peptides (FIG. 2F) for four example proteinsshowing strong preferential enrichment by one FFF probe over control 1(FIG. 2D) and the corresponding results for these proteins inprobe-vs-probe experiments (FIG. 2E). FIG. 2G exemplifies that themajority of proteins that are strongly enriched (SILAC ratio>10) by mostFFF probes (≥8 of 11) in probe-vs-control 1 experiments showpreferential enrichment by one FFF probe in probe-vs-probe experiments.(FIG. 2H-FIG. 2J) Heatmaps (FIG. 2H, FIG. 2I) and extracted MS1chromatograms of representative tryptic peptides (FIG. 2J) for threeexample proteins showing enrichment by the majority of FFF probes overcontrol 1 (FIG. 2H) and preferential enrichment by FFF probe 3 inprobe-vs-probe experiments (FIG. 2I). FIG. 2K exemplifies that FFFprobes show minimal toxicity in HEK293T cells when tested underconditions that mirror those used for mapping probe-protein interactionsin cells (200 μM FFF probe, 45 min incubation). Viability was assessedby CellTiter-Glo luminescent assay. Data represent average values±SD.n=3 per group. FIG. 2L exemplifies SILAC ratio plots for representativeFFF probes in which isotopically heavy and light amino acid-labeledHEK293T cells were treated with control 1 or the indicated FFF probe(200 μM each). Dashed line indicates required threshold enrichment ratio(>5-fold) for designation of FFF targets. FIG. 2M exemplifiesrepresentative SILAC ratio plots for control experiments in whichisotopically heavy and light amino acid-labeled HEK293T cells weretreated with the same FFF probe (200 μM). FIG. 2N exemplifies thatfraction of targets for representative FFF probes that exhibitUV-dependent enrichment. Briefly, ‘light’ cells were treated with 200 μMof the corresponding probe and UV-irradiated while ‘heavy’ cells weretreated with the same probe and not exposed to UV light. Proteins wereconsidered to be labeled in a UV-dependent fashion if >3-fold enrichmentin light cells was observed. For each probe, >97% of protein targetsexhibited UV-dependent enrichment. FIG. 2O exemplifies the number ofprotein targets enriched by corresponding FFF probes tested at 20 and200 μM. (FIG. 2P) Heatmap of enriched proteins in FFFprobe-versus-control 1 experiments using 20 μM FFF in HEK293T cells.FIG. 2Q exemplifies histogram of HEK293T cell-derived iBAQ values asestimates of the abundance distribution for protein targets of FFFprobes. FIG. 2R exemplifies box-and-whisker plot of iBAQ values for FFFprotein targets plotted versus the number of FFF probes that enrichedeach protein (□=Spearman's correlation coefficient). FIG. 2S exemplifieshistogram showing the number of FFF probe hits per protein target; amedian value of three probes were found per protein. FIG. 2T exemplifiesconfirmation of FFF probe interaction profiles for representativeprotein targets. Proteins were recombinantly expressed as FLAG-taggedforms in HEK293T cells, followed by treatment with the indicated FFFprobes (20 μM), photocrosslinking and lysis, SDS-PAGE, and in-gelfluorescence scanning. FIG. 2U exemplifies that for proteins shown inFIG. 2T, extracted MS1 chromatograms and corresponding SILAC ratios ofrepresentative tryptic peptides quantified in the indicatedprobe-versus-probe experiments.

FIG. 3A-FIG. 3P exemplify types of proteins and sites on these proteinstargeted by FFF probes. (FIG. 3A, FIG. 3B) Categorization of FFF probetargets based on presence or absence in DrugBank (FIG. 3A) and proteinclass distribution (FIG. 3B). FIG. 3C exemplifies the number of FFFprobe-modified peptides per protein target. FIG. 3D represents thedistribution of probe-modified peptides that overlap (or do not overlap)with residues in predicted binding pockets of proteins with structuresavailable in the PDB (as determined by fpocket analysis). (FIG. 3E-FIG.3G) Examples of probe labeling sites mapped onto protein structures.Tryptic peptides containing probe-labeled sites are shown in green, andresidues that overlap with predicted binding pockets are shown in beige.FIG. 3E exemplifies that FFF 13-modified peptide (aa 197-215) in humanYWHAE (gray, PDB 3UBW) overlaps with the binding cleft that interactswith myeloid leukemia factor 1 (MLF1-derived peptide shown in yellow).This pocket is also the target of fragment (3S)-pyrrolindin-3-ol shownin purple. FIG. 3E discloses SEQ ID NO: 918. FIG. 3F exemplifies thatFFF 13-modified peptide (aa 66-79) in human BAX (gray, PDB 4ZIE)complexed with BH3 peptide of BIM (cyan). FIG. 3F discloses SEQ ID NO:919. FIG. 3G exemplifies the ribbon structure of human CTSB (gray, PDB1GMY) highlighting FFF 9-modified peptide (aa 315-332) that is competedwhen HEK293T cells are co-treated with 9 (200 μM) and CTSB inhibitorZ-FA-FMK. Represented in yellow is the catalytic cysteine C108 (red)bound to Z-FA-FMK. FIG. 3G discloses SEQ ID NO: 920. FIG. 3H exempliesthat fraction of FFF probe targets with (membrane) or without (soluble)known/predicted transmembrane domains. FIG. 3I exemplifies the breakdownof soluble and membrane proteins, and corresponding probe-modifiedpeptides from these proteins, with available crystal structures. FIG. 3Jexemplifies the distribution of peptides labeled by one or more FFFprobes. FIG. 3K exemplifies the distribution of probe-modified peptidesbased on overlap of their amino acid sequence with predicted bindingpocket residues determined by fpocket analysis. FIG. 3L exemplifies thefraction of proteins with multiple probe-modified peptides thatcorrespond to shared or distinct binding pockets. FIG. 3M exemplifiesfor proteins with annotated functional sites, distances of functionalsites from probe-modified peptides. Functional sites include annotatedenzyme catalytic residues (active sites), substrate binding sites, andmetal-binding sites. FIG. 3N exemplifies the functional classdistribution for proteins with FFF-modified peptides and subdividedbased on availability of crystal structures for these proteins. FIG. 3Oexemplifies FFF 9-modified peptides (green/tan, where tan furtherdesignates residues that overlap with those predicted to be part ofbinding pockets as determined by fpocket) in the structure of human GLA(gray, PDB 3S5Z). Peptides aa 50-68 and aa 241-253 are found near theactive site (purple, with substrate alpha D-galactose depicted inyellow) and a secondary ligand binding site (with the beta D-galactoseligand depicted in yellow), respectively. FIG. 3O discloses SEQ ID NOS921-922, respectively, in order of appearance. FIG. 3P exemplifiesoverlap of protein targets of FFF probes with protein targets ofcysteine-reactive fragments.

FIG. 4A-FIG. 4M exemplify ligand discovery by competitive profiling ofelaborated fragment-based compounds. FIG. 4A exemplifies a schematic forcompetitive profiling experiments. Isotopically heavy and light aminoacid-labeled cells are treated with DMSO or elaborated fragmentcompetitor, respectively, and the corresponding FFF probe for 30 min,followed by UV light exposure, cell lysis, CuAAC conjugation to biotinazide, streptavidin enrichment of probe-labeled proteins, trypticdigestion, and quantitative MS analysis of tryptic peptides. Competedtargets are defined as those showing >3-fold reductions in FFF probelabeling in the presence of competitor compound. FIG. 4B exemplifiesstructure of fragment cores (upper) with representative elaboratedcompetitors (lower, where core fragments are depicted). (FIG. 4C, FIG.4D) Heatmap of (FIG. 4C) and number of competitor compounds per (FIG.4D) competed protein targets in experiments using 20 μM FFF and 160 μMcompetitor. FIG. 4E exemplifies categorization of competed targets basedon presence or absence in DrugBank for experiments using either 20 μMFFF probes (+160 μM competitors) or 200 μM FFF probes (+200 μMcompetitors). Targets competed in both 20 and 200 μM data sets wereexcluded from the 200 μM groups for the pie chart analysis. FIG. 4Fexemplifies the protein functional class distribution for competedtargets compared to all FFF probe targets. (FIG. 4G, FIG. 4H)Representative SILAC ratio plots for competitive profiling experimentswith FFF probes 8 (FIG. 4G) and 3 (FIG. 4H) (20 μM) and 8× competitors20 and 21, respectively. PTGR2 (FIG. 4G) and SLC25A20 (FIG. 4H) wereidentified as the top competed targets for 20 and 21, respectively.Dotted lines indicate a three-fold ratio change threshold fordesignating competed targets. (FIG. 4I-FIG. 4K) Structures of elaboratedfragment competitors with corresponding FFF probe used in competitiveprofiling experiments. Core fragment structure within each competitorcompound is highlighted. FIG. 4L exemplifies the number of competedprotein targets per competitor tested in HEK293T cells at 160 μM with 20μM FFF probe. FIG. 4M exemplifies the total number of competed proteintargets for five representative competitors (160-200 μM) evaluated inexperiments with high (200 μM) or low (20 μM) concentrations of FFFprobes.

FIG. 5A-FIG. 5S exemplify fragment-derived ligands disrupt function ofPTGR2 and SLC25A20 in human cells. FIG. 5A exemplifies structure ofhPTGR2 (PDB 2ZB4, gray) highlighting FFF 8-modified tryptic peptides (aa55-66, green; and aa 261-278, pink) near the active site (15-keto-PGE2in yellow, NADP+ in blue) of PTGR2. Probe labeling (200 μM) of bothtryptic peptides was blocked by 20 (200 μM), as shown withrepresentative MS1 plots for each peptide. FIG. 5A discloses SEQ ID NOS923-924, respectively, in order of appearance. FIG. 5B exemplifies PTGR2ligands 22 and 20 but not inactive control 23, inhibited 15-ketoprostaglandin E2 (15-keto-PGE2) reductase activity of recombinant PTGR2.Data represent average values±SD; n=3 per group. FIG. 5C exemplifiesstructures (top) and activities (bottom gels) of initial PTGR2 ligand20, optimized ligand 22, and inactive analog 23. Gels showconcentration-dependent competitor blockade of FFF 8 labeling ofrecombinantly expressed FLAG-tagged PTGR2 in HEK29T cells. FIG. 5Dexemplifies compound 22, but not inactive control 23, increased15-keto-PGE2-dependent PPARγ transcriptional activity inPTGR2-transfected HEK293T cells. Data represent average values±SD;####p<0.0001 for 15k-PGE2-treated PTGR2-transfected cells versus emptyvector group, ****p<0.0001 for compound- versus DMSO-treated groups; n=3per group. FIG. 5E exemplifies structures (top) and activities (bottomgels) of SLC25A20 ligand 21 and inactive analog 24. Gel showsconcentration-dependent competitor blockade of FFF 3 labeling (20 μM) ofrecombinantly expressed FLAG-tagged SLC25A20 in HEK29T cells. (FIG. 5F,FIG. 5G) Compound 21, but not 24, increases long-chain (>C14)acylcarnitine content (FIG. 5F) and reduces maximal exogenous fatty acidoxidation (FIG. 5G) of HSC-5 cells. Data represent average values±SD;**p<0.01 and ****p<0.0001 for compound- versus DMSO-treated groups;n=3-5 per group. FIG. 5H exemplifies expanded screen of competitorcompounds by monitoring reductions in FFF probe labeling ofrecombinantly expressed, FLAG-tagged human PTGR2 and SLC25A20 in HEK293Tcells. FIG. 5I exemplifies competition gel profiles for competitorcompounds corresponding to fragment elements from FFF probes 8(competitor 49 for PTGR2) and 3 (competitor 50 for SLC25A20). FIG. 5Jexemplifies optimization of PTGR2 inhibitors. Upper images showstructures of analogs of lead inhibitor 20 that were synthesized andtested. Lower image shows competition gel profiles for these analogswith human PTGR2 expressed in HEK293T cells. FIG. 5K exemplifiesextracted MS1 chromatograms and corresponding SILAC ratios forrepresentative tryptic peptides of PTGR2 from competition experimentswith the indicated compounds, in which isotopically light and heavyamino acid-labeled HEK293T cells were treated with FFF probe 8 (20 μM)and, respectively, DMSO (red) or competitor compound (blue) at theindicated concentrations. (FIG. 5L, FIG. 5M) Competition SILAC plots foroptimized PTGR2 inhibitor 22 (60 μM, FIG. 5L) and inactive control 23(160 μM, FIG. 5M) tested with FFF probe 8 (20 μM). FIG. 5N exemplifiesPTGR2 ligands 20 and 22 do not directly induce PPARγ transcriptionalactivity in HEK293T cells co-transfected with a GAL4-PPARγ luciferasereporter and an empty control vector. FIG. 5O exemplifies fitted fulldose-response of data exemplified in FIG. 5D. FIG. 5P exemplify fittedIC₅₀ curve for the concentration-dependent blockade of 3 (20 μM)labeling of SLC25A20 expressed in HEK293T cells by 21 withrepresentative competition gel shown below. Data represent averagevalues±SD; n=3 per group. FIG. 5Q exemplify extracted MS1 chromatogramsand corresponding SILAC ratios for representative tryptic peptides ofSLC25A20 from competition experiments with the indicated compounds atthe indicated concentrations. FIG. 5R exemplify competition SILAC plotsfor inactive control 24 (160 μM) tested with FFF probe 3 (20 μM). FIG.5S exemplify oxygen consumption rate (OCR) of HSC5 cells pre-treated for40 min with 21 or 24 and then provided with exogenous palmitate. Aconcentration-dependent inhibition of basal and maximal respiration wasobserved for 21, but not 24. Data represent average values±SD; n=5 pergroup. Oligomycin is an inhibitor of ATP synthase; FCCP=carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone is an ionophore uncouplingreagent that collapses mitochondrial membrane potential, allowingmaximal respiration; RAA=rotenone and antimycin A are complex I andcomplex III inhibitors that block mitochondrial respiration, enablingthe calculation of non-mitochondrial respiration.

FIG. 6A-J illustrates additional small molecule ligands substituentsdisclosed herein.

DETAILED DESCRIPTION OF THE DISCLOSURE

Chemical probes can be discovered through multiple routes that caninvolve, for example, high-throughput screening (HTS) of individualproteins (target-based) or more complex cell and organismal systems(e.g., phenotype-based systems). In some instances, high-throughputscreening, whether it is target- or phenotype-based, uses large chemicallibraries (˜10⁶) composed of relatively high MW (300-500 Da) andstructurally diverse compounds. In some cases, hit compounds from theselibraries prove difficult to optimize due to their size, structuralcomplexity, and suboptimal ligand efficiency. Target-based screens arefurthermore generally performed with purified proteins and therefore donot provide direct information about the activity of ligands in morecomplex biological systems (e.g., cells), where factors that regulateprotein structure and function, such as subcellular localization,post-translational modification, and protein-protein interactions canaffect ligand-protein interactions. Alternatively, phenotype-basedscreening, for example, faces the challenge of identifying the moleculartarget(s) of active compounds, in particular, in cases where thescreening hits display moderate-low potency.

Fragment-based ligand and drug discovery (FBLD) is an approach thatutilizes smaller numbers (˜10³) of low molecular weight compounds (<300Da), and typically screened at high concentrations (>100 M). In someinstances, FBLD emphasizes the identification of structurally simple hitcompounds that are then optimized into more potent ligands. In somecases, a tenet of FBLD is that, by limiting molecular size, a relativelysmall number of fragments can represent a large fraction of accessiblechemical space.

In some embodiments, described herein is another method of identifyingsmall molecule ligands for interaction with target proteins of interest.In some instances, this method allows for mapping of small moleculeligands for interaction with a target protein under native conditions,thereby allowing for accurate mapping of interaction with potentialsmall molecule ligands. In some instances, the method allows foridentification of novel proteins as druggable targets as the methodeliminates the need of recombinant expression and purification.

In additional embodiments, described herein include small moleculeligands, compositions, cells and assays related to the method ofidentifying small molecule ligands for interaction with target proteinsof interest.

Small Molecule Ligands

In some embodiments, disclosed herein are small molecule ligands inwhich each of the small molecule ligand comprises a photoreactivediazirine group and an alkyne group. In some instances, the alkyne groupis a terminal alkyne group. In some instances, the small molecule ligandfurther comprises a small molecule fragment. In some embodiments, thesmall molecule fragments described herein comprise non-naturallyoccurring molecules. In some instances, the non-naturally occurringmolecules do not include natural and/or non-natural peptide fragments,or small molecules that are produced naturally within the body of amammal.

In some embodiments, a small molecule fragment described hereincomprises a molecule weight of about 100 Dalton or higher. In someembodiments, the small molecule fragment comprises a molecule weight ofabout 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240,250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380,390, 400, 410, 420, 430, 440, 450, 500, 550, 600, 650, 700, 750, 800,850, 900, 950, 1000 Dalton, or higher. In some instances, the moleculeweight of the small molecule fragment is between about 150 and about500, about 150 and about 450, about 150 and about 440, about 150 andabout 430, about 150 and about 400, about 150 and about 350, about 150and about 300, about 150 and about 250, about 170 and about 500, about180 and about 450, about 190 and about 400, about 200 and about 350,about 130 and about 300, or about 120 and about 250 Dalton.

In some embodiments, the molecule weight of a small molecule fragmentdescribed herein is calculated based on the molecule weight of carbonand hydrogen atoms and optionally further based on nitrogen, oxygenand/or sulfur atoms of the small molecule fragment. In some cases, themolecule weight of the small molecule fragment is calculated without themolecular weight of one or more elements selected from a halogen, anonmetal, a transition metal, or a combination thereof.

In some embodiments, a small molecule fragment described hereincomprises micromolar or millimolar binding affinity. In some instances,the small molecule fragment comprises a binding affinity of about 100nM, 200 nM, 300 nM, 400 nM, 500 nM, 1 μM, 10 μM, 100 μM, 500 μM, 1 mM,10 mM, or higher.

In some embodiments, a small molecule fragment described herein has ahigh ligand efficiency (LE). Ligand efficiency is the measurement of thebinding energy per atom of a ligand to its binding partner. In someinstances, the ligand efficiency is defined as the ratio of the Gibbsfree energy (ΔG) to the number of non-hydrogen atoms of the compound(N):LE=(ΔG)/N.

In some cases, LE is also arranged as:LE=1.4(−log IC₅₀)/N.

In some instances, the LE score is about 0.3 kcal mol⁻¹HA⁻¹, about 0.35kcal mol⁻¹HA⁻¹, about 0.4 kcal mol⁻¹HA⁻¹, or higher.

In some embodiments, a small molecule fragment described herein isdesigned based on the Rule of 3. In some embodiments, the Rule of 3comprises a non-polar solvent-polar solvent (e.g. octanol-water)partition coefficient log P of about 3 or less, a molecular mass ofabout 300 Daltons or less, about 3 hydrogen bond donors or less, about 3hydrogen bond acceptors or less, and about 3 rotatable bonds or less.

In some embodiments, a small molecule fragment described hereincomprises three cyclic rings or less.

In some embodiments, a small molecule fragment described herein binds toa binding site of a protein in which the protein is about 20 amino acidresidues in length or more. In some instances, the small moleculefragment described herein binds to a binding site of a protein in whichthe protein is about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900,1000 amino acid residues in length or more.

In some embodiments, a small molecule fragment described herein isobtained from a compound library. In some cases, the compound librarycomprises ChemBridge fragment library, Pyramid Platform Fragment-BasedDrug Discovery, Maybridge fragment library, FRGx from AnalytiCon,TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D fromCharles River, Fragments of Life (FOL) from Emerald Bio, EnamineFragment Library, IOTA Diverse 1500, BIONET fragments library, LifeChemicals Fragments Collection, OTAVA fragment library, Prestwickfragment library, Selcia fragment library, TimTec fragment-basedlibrary, Allium from Vitas-M Laboratory, or Zenobia fragment library.

In some embodiments, a small molecule fragment comprises a structureillustrated in FIG. 1B, in which each fragment nomenclature (or probenomenclature) is illustrated by a numerical number. For example, thesmall molecule fragment

is assigned as probe 1.

In some embodiments, a small molecule ligand described herein has astructure represented by Formula (I):

wherein R is selected from the groups provided below:

Protein Targets

In some embodiments, a protein target described herein is a solubleprotein or a membrane protein. In some cases, a protein target describedherein is involved in one or more of a biological process such asprotein transport, lipid metabolism, apoptosis, transcription, electrontransport, mRNA processing, or host-virus interaction. In someinstances, the protein target is associated with one or more of diseasessuch as cancer or one or more disorders or conditions such as immune,metabolic, developmental, reproductive, neurological, psychiatric,renal, cardiovascular, or hematological disorders or conditions.

In some embodiments, the protein target comprises one or more functionsof an enzyme, a transporter, a receptor, a channel protein, an adaptorprotein, a chaperone, a signaling protein, a plasma protein,transcription related protein, translation related protein,mitochondrial protein, or cytoskeleton related protein. In someembodiments, the protein target is an enzyme, a transporter, a receptor,a channel protein, an adaptor protein, a chaperone, a signaling protein,a plasma protein, transcription related protein, translation relatedprotein, mitochondrial protein, or cytoskeleton related protein. In someinstances, the protein target has an uncategorized function.

In some embodiments, the protein target is an enzyme. An enzyme is aprotein molecule that accelerates or catalyzes chemical reaction. Insome embodiments, non-limiting examples of enzymes include kinases,proteases, or deubiquitinating enzymes.

In some instances, exemplary kinases include tyrosine kinases such asthe TEC family of kinases such as Tec, Bruton's tyrosine kinase (Btk),interleukin-2-indicible T-cell kinase (Itk) (or Emt/Tsk), Bmx, andTxk/Rlk; spleen tyrosine kinase (Syk) family such as SYK andZeta-chain-associated protein kinase 70 (ZAP-70); Src kinases such asSrc, Yes, Fyn, Fgr, Lck, Hck, Blk, Lyn, and Frk; JAK kinases such asJanus kinase 1 (JAK1), Janus kinase 2 (JAK2), Janus kinase 3 (JAK3), andTyrosine kinase 2 (TYK2); or ErbB family of kinases such as Her1 (EGFR,ErbB1), Her2 (Neu, ErbB2), Her3 (ErbB3), and Her4 (ErbB4).

In some embodiments, the protein target is a protease. In someembodiments, the protease is a caspase. In some instances, the caspaseis an initiator (apical) caspase. In some instances, the caspase is aneffector (executioner) caspase. Exemplary caspase includes CASP2, CASP8,CASP9, CASP10, CASP3, CASP6, CASP7, CASP4, and CASP5. In some instances,the cysteine protease is a cathepsin. Exemplary cathepsin includesCathepsin B, Cathepsin C, Cathepsin F, Cathepsin H, Cathepsin K,Cathepsin L1, Cathepsin L2, Cathepsin O, Cathepsin S, Cathepsin W, orCathepsin Z.

In some embodiments, the protein target is a deubiquitinating enzyme(DUB). In some embodiments, exemplary deubiquitinating enzymes includecysteine proteases DUBs or metalloproteases. Exemplary cysteine proteaseDUBs include ubiquitin-specific protease (USP/UBP) such as USP1, USP2,USP3, USP4, USP5, USP6, USP7, USP8, USP9X, USP9Y, USP10, USP11, USP12,USP13, USP14, USP15, USP16, USP17, USP17L2, USP17L3, USP17L4, USP17L5,USP17L7, USP17L8, USP18, USP19, USP20, USP21, USP22, USP23, USP24,USP25, USP26, USP27X, USP28, USP29, USP30, USP31, USP32, USP33, USP34,USP35, USP36, USP37, USP38, USP39, USP40, USP41, USP42, USP43, USP44,USP45, or USP46; ovarian tumor (OTU) proteases such as OTUB1 and OTUB2;Machado-Josephin domain (MJD) proteases such as ATXN3 and ATXN3L; andubiquitin C-terminal hydrolase (UCH) proteases such as BAP1, UCHL1,UCHL3, and UCHL5. Exemplary metalloproteases include the Jab1/Mov34/Mpr1Pad1 N-terminal+ (MPN+) (JAMM) domain proteases.

In some embodiments, exemplary proteins as enzymes include, but are notlimited to, abhydrolase domain-containing protein 10, mitochondrial(ABHD10); aconitate hydratase, mitochondrial (ACO2); low molecularweight phosphotyrosine protein phosphatase (ACP1); chaperone activity ofbeI complex-like, mitochondrial (ADCK3); adenosine kinase (ADK);adenylosuccinate synthetase isozyme 2 (ADSS); acylglycerol kinase,mitochondrial (AGK); alkyldihydroxyacetonephosphate synthase,peroxisomal (AGPS); apoptosis-inducing factor 1, mitochondrial (AIFM1);Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1); mitochondrial10-formyltetrahydrofolate dehydrogen (ALDHIL2); alpha-aminoadipicsemialdehyde dehydrogenase (ALDH7A1); ATPase ASNAI (ASNAI); ATPasefamily AAA domain-containing protein 3A (ATAD3A); bifunctional purinebiosynthesis protein PURH (ATIC); bleomycin hydrolase (BLMH); calpain-1catalytic subunit (CAPN1); creatine kinase B-type (CKB); caseinolyticpeptidase B protein homolog (CLPB); putative ATP-dependent Clp proteaseproteolytic subunit (CLPP); carnitine O-palmitoyltransferase 2,mitochondrial (CPT2); probable serine carboxypeptidase CPVL (CPVL);cathepsin B (CTSB); cathepsin D (CTSD); NADH-cytochrome b5 reductase 3(CYB5R3); cytochrome P450 20A1 (CYP20A1); 2,4-dienoyl-CoA reductase,mitochondrial (DECR1); delta(24)-sterol reductase (DHCR24);dihydrolipoyl dehydrogenase, mitochondrial (DLD);deoxyribonuclease-2-alpha (DNASE2); endothelin-converting enzyme 1(ECEI); Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial(ECH1); eukaryotic translation initiation factor 3 subunit (EIF3F);elongation of very long chain fatty acids protein (ELOVL2); exonuclease1 (EXO1); phenylalanine—tRNA ligase beta subunit (FARSB); fatty acidsynthase (FASN); squalene synthase (FDFT1); ferrochelatase,mitochondrial (FECH); alpha-galactosidase A (GLA); beta-galactosidase(GLB1); lactoylglutathione lyase (GLO1); glutamate dehydrogenase 1,mitochondrial (GLUD1); hydroxyacyl-coenzyme A dehydrogenase,mitochondrial (HADH); trifunctional enzyme subunit alpha, mitochondrial(HADHA); histidine—tRNA ligase, cytoplasmic (HARS); minorhistocompatibility antigen H13 (HM13); heme oxygenase 2 (HMOX2);estradiol 17-beta-dehydrogenase 12 (HSD17B12); peroxisomalmultifunctional enzyme type 2 (HSD17B4); insulin-degrading enzyme (IDE);isocitrate dehydrogenase (IDH2); gamma-interferon-inducible lysosomalthiol reductase (IFI30); inosine-5-monophosphate dehydrogenase 2(IMPDH2); leucine—tRNA ligase, cytoplasmic (LARS); L-lactatedehydrogenase A chain (LDHA); L-lactate dehydrogenase B chain (LDHB);legumain (LGMN); lysosomal acid lipase/cholesteryl ester hydrolase(LIPA); methyltransferase-like protein 7A (METTL7A); NADH-ubiquinoneoxidoreductase chain 2 (MT-ND2); monofunctional C1-tetrahydrofolatesynthase, mitochondrial (MTHFDIL); alpha-N-acetylglucosaminidase(NAGLU); peroxisomal NADH pyrophosphatase NUDT12 (NUDT12); nucleosidediphosphate-linked moiety X motif 19, mitochondrial (NUDT19); ornithineaminotransferase, mitochondrial (OAT); phosphoenolpyruvate carboxykinase(PCK2); protein-L-isoaspartate(D-aspartate)O-methyltransferase (PCMT1);prenylcysteine oxidase 1 (PCYOX1); presequence protease, mitochondrial(PITRM1); pyruvate kinase isozymes M1/M2 (PKM); peroxiredoxin-2 (PRDX2);DNA-dependent protein kinase catalytic subunit (PRKDC); proteasomesubunit alpha type-2 (PSMA2); dolichyl-diphosphooligosaccharide—proteinglycosyltransferase subnit 1 (RPN1); RuvB-like 1 (RUVBL1); thimetoligopeptidase (THOP1); or tripeptidyl-peptidase 1 (TPP1).

In some embodiments, the protein target is a transcription factor orregulator. Exemplary protein targets as transcription factors andregulators include, but are not limited to, actin-like protein 6A(ACTL6A); putative adenosylhomocysteinase 2 (AHCYL1); acidicleucine-rich nuclear phosphoprotein 32 family member A (ANP32A);complement component 1 Q subcomponent-binding protein (C1QBP); probableATP-dependent RNA helicase DDX17 (DDX17); probable ATP-dependent RNAhelicase DHX36 (DHX36); elongation factor 1-alpha 1 (EEF1A1); eukaryoticinitiation factor 4A-I (EIF4A1); electron transfer flavoprotein subunitbeta (ETFB); far upstream element-binding protein 1 (FUBP1); histoneH1.2 (HIST1H1C); heterogeneous nuclear ribonucleoprotein K (HNRNPK);interleukin enhancer-binding factor 2 (ILF2); DNA replication licensingfactor MCM2 (MCM2); DNA replication licensing factor MCM4 (MCM4);N-alpha-acetyltransferase 15, NatA auxiliary subunit (NAA15); non-POUdomain-containing octamer-binding protein (NONO); nucleobindin-1 (UCB1);polyadenylate-binding protein 1 (PABPC1); paraspeckle component 1(PSPC1); RNA-binding protein 14 (RBM14); putative RNA-binding protein 3(RBM3); RNA-binding motif protein, X chromosome (RBMX); 40S ribosomalprotein S3 (RPS3); X-ray repair cross-complementing protein 6 (XRCC6);nuclease-sensitive element-binding protein 1 (YBX1); prostaglandinreductase 2 (PTGR2); zinc binding alcohol dehydrogenase domaincontaining 2 (ZADH2); or lysophosphatidylcholine acetyltransferase 3(LPCAT3).

In some embodiments, the protein target is a channel, transporter orreceptor. Exemplary protein targets as channels, transporters, orreceptors include, but are not limited to, alpha-actinin-4 (ACTN4); AP-1complex subunit beta-1 (AP1B1); ADP-ribosylation factor 1 (ARF1);ADP-ribosylation factor 3 (ARF3); ADP-ribosylation factor 4 (ARF4);ADP-ribosylation factor 5 (ARF5); sodium/potassium-transporting ATPasesubunit alpha (ATP1A1); sarcoplasmic/endoplasmic reticulum calciumATPase (ATP2A2); plasma membrane calcium-transporting ATPase 1 (ATP2B1);plasma membrane calcium-transporting ATPase 4 (ATP2B4); ATP synthasesubunit alpha, mitochondrial (ATP5A1); coatomer subunit beta (COPB1);exportin-2 (CSE1L); Electron transfer flavoprotein subunit beta (ETFB);heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1); heterogeneousnuclear ribonucleoprotein A1-like 2 (HNRNPA1L2); importin-4 (IPO4);cytochrome c oxidase subunit 2 (MT-C02); nuclear autoantigenic spermprotein (NASP); nucleoporin Nup37 (NUP37); nuclear pore complex proteinNup93 (NUP93); nuclear transport factor 2 (NUTF2); membrane-associatedprogesterone receptor component (PGRMC2); prohibitin-2 (PHB2); proteinquaking (QKI); sideroflexin-1 (SFXN1); ADP/ATP translocase 3 (SLC25A6);mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20) orvoltage-dependent anion-selective channel protein (VDAC3).

In some embodiments, the protein target is a chaperone. Exemplaryprotein targets as chaperones include, but are not limited to, acidicleucine-rich nuclear phosphoprotein 32 family member B (ANP32B); largeproline-rich protein BAG6 (BAG6); T-complex protein 1 subunit beta(CCT2); peptidyl-prolyl cis-trans isomerase FKBP4 (FKBP4); heat shockprotein HSP 90-beta (HSP90AB1); endoplasmin (HSP90B1); LDLR chaperoneMESD (MESDC2); nucleophosmin (NPM1); or protein SET (SET).

In some embodiments, the protein target is an adapter, scaffolding ormodulator protein. Exemplary protein targets as adapter, scaffolding, ormodulator proteins include, but are not limited to, actin, alphaskeletal muscle (ACTA1); actin, cytoplasmic 1 (ACTB);cytoskeleton-associated protein 4 (CKAP4); cytochrome c oxidase subunit5A, mitochondrial (COX5A); catenin beta-1 (CTNNB1); FGFR1 oncogenepartner (FGFR1OP); HAUS augmin-like complex subunit 2 (HAUS2);hemoglobin subunit alpha (HBA2); kinesin-like protein KIF11 (KIF11);myosin-10 (MYH10); myosin-9 (MYH9); phosphatidylinositol transferprotein beta isoform (PITPNB); proactivator polypeptide (PSAP);endophilin-B1 (SH3GLB1); stomatin-like protein 2 (STOML2); tubulinbeta-4B chain (TUBB4B); or tubulin beta-6 chain (TUBB6).

In some embodiments, a protein target comprises a protein illustrated inTables 1-4. In some instances, a protein target comprises a proteinillustrated in Table 1. In some embodiments, the protein targetcomprises a binding site denoted in Table 1. In some instances, aprotein target comprises a protein illustrated in Table 2. In someembodiments, the protein target comprises a binding site denoted inTable 2. In some instances, a protein target comprises a proteinillustrated in Table 3. In some embodiments, the protein targetcomprises a binding site denoted in Table 3. In some instances, aprotein target comprises a protein illustrated in Table 4.

Methods of Use

In some embodiments, disclosed herein include a method of identifying aprotein that is capable of interacting with a small molecule ligand. Insome instances, the method comprises (a) providing a cell sample; (b)exposing the cell sample to a plurality of potential small moleculeligands having a structure comprising at least a photoreactive diazirinegroup and a terminal alkyne group; (c) irradiating the cell sample withUV light; (d) performing lysis on the cell sample; (e) subjectingproteins in the post lysis material to fluorophore tagging (e.g.,rhodamine, fluorescein, and the like); and (f) isolating at least onefluorophore-tagged protein. In other instances, the method comprises (a)providing a cell sample; (b) exposing the cell sample to the smallmolecule ligand having a structure comprising at least a photoreactivediazirine group, and a terminal alkyne group; (c) irradiating the cellsample with UV light; (d) performing lysis on the cell sample; (e)subjecting the proteins in the post lysis material to tagging; and (f)isolating the tagged proteins for analysis to identify a protein capableof interacting with the small molecule ligand.

In some cases, the small molecule ligand has a structure represented byFormula (I):

wherein R is selected from the groups provided below:

In some cases, the small molecule ligand has a structure represented byFormula (Ib):

wherein R is an amide substituent bonded to the NH group of the aminesprovided in FIGS. 6A-J.

In some cases, the small molecule ligand has a structure represented byFormula (II):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (III):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (III):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (IV):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (V):

wherein R¹ is selected from substituted alkyl, optionally substitutedaryl, optionally substituted heteroaryl, optionally substitutedcycloalkyl, optionally substituted heterocyclyl, optionally substitutedheteroaryl, optionally substituted aralkyl, optionally substitutedheteroarylalkyl, or optionally substituted heterocyclylalkyl.

In some cases, the small molecule ligand has a structure represented byFormula (VI):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the tagging further comprises i) attaching the smallmolecule ligand-protein complex to a biotin moiety and ii) interactingthe biotin moiety with a streptavidin-coupled bead.

In some instances, the analysis comprises a proteomic analysis.

In some instances, a cell from the cell sample is a mammalian cell. Insome cases, a cell from the cell sample is obtained from HEK293T, K562,or HSC-5 cell lines. In some cases, a cell from the cell sample is atumor cell.

In some cases, the method is an in situ method. In other cases, themethod is an in vitro method.

In some embodiments, also disclosed herein include a method ofidentifying a small molecule ligand binding site on an isolated protein.In some cases, the method comprises (a) providing an isolated protein;(b) exposing the protein to a plurality of potential small moleculeligands having a structure comprising at least a photoreactive diazirinegroup and a terminal alkyne group; (c) irradiating the protein with UVlight; (d) tagging the protein with biotin; (e) binding thebiotin-tagged protein to solid phase beads; (f) digesting the protein toprovide protein fragments; and (g) analyzing the protein fragments todetermine the small molecule ligand binding site.

In some instances, the isolated protein is selected from Tables 1-3. Insome cases, the isolated protein is selected from Table 1. In somecases, the isolated protein is selected from Table 2. In some cases, theisolated protein is selected from Table 3. In some cases, the isolatedprotein is a recombinant protein.

In some cases, the small molecule ligand has a structure represented byFormula (I):

wherein R is selected from the groups provided below:

In some cases, the small molecule ligand has a structure represented byFormula (Ib):

wherein R is an amide substituent bonded to the NH group of the aminesprovided in FIGS. 6A-J.

In some cases, the small molecule ligand has a structure represented byFormula (II):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (III):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (III):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (IV):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some cases, the small molecule ligand has a structure represented byFormula (V):

wherein R¹ is selected from substituted alkyl, optionally substitutedaryl, optionally substituted heteroaryl, optionally substitutedcycloalkyl, optionally substituted heterocyclyl, optionally substitutedheteroaryl, optionally substituted aralkyl, optionally substitutedheteroarylalkyl, or optionally substituted heterocyclylalkyl.

In some cases, the small molecule ligand has a structure represented byFormula (VI):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring.

In some instances, the analyzing comprises a proteomic analysis.

In some embodiments, tagging comprises labeling the protein with alabeling group for use in further analysis of the protein. In someinstances, the labeling group comprises a fluorophore. In someinstances, a fluorophore comprises rhodamine, rhodol, fluorescein,thiofluorescein, aminofluorescein, carboxyfluorescein,chlorofluorescein, methylfluorescein, sulfofluorescein, aminorhodol,carboxyrhodol, chlororhodol, methylrhodol, sulforhodol, aminorhodamine,carboxyrhodamine, chlororhodamine, methylrhodamine, sulforhodamine,thiorhodamine, cyanine, indocarbocyanine, oxacarbocyanine,thiacarbocyanine, merocyanine, cyanine 2, cyanine 3, cyanine 3.5,cyanine 5, cyanine 5.5, cyanine 7, oxadiazole derivatives,pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, pyren derivatives,cascade blue, oxazine derivatives, Nile red, Nile blue, cresyl violet,oxazine 170, acridine derivatives, proflavin, acridine orange, acridineyellow, arylmethine derivatives, auramine, crystal violet, malachitegreen, tetrapyrrole derivatives, porphin, phtalocyanine, bilirubin1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalene sulfonate,2-p-touidinyl-6-naphthalene sulfonate, 3-phenyl-7-isocyanatocoumarin,N-(p-(2-benzoxazolyl)phenyl)maleimide, stilbenes, pyrenes, 6-FAM(Fluorescein), 6-FAM (NHS Ester), 5(6)-FAM, 5-FAM, Fluorescein dT,5-TAMRA-cadavarine, 2-aminoacridone, HEX, JOE (NHS Ester), MAX, TET,ROX, TAMRA, TARMA™ (NHS Ester), TEX 615, ATTO™ 488, ATTO™ 532, ATTO™550, ATTO™ 565, ATTO™ Rho101, ATTO™ 590, ATTO™ 633, ATTO™ 647N, TYE™563, TYE™ 665, or TYE™ 705.

In some embodiments, the labeling group comprises a biotin, astreptavidin, bead, resin, a solid support, or a combination thereof. Asused herein, a biotin described herein comprises biotin and biotinderivatives. Exemplary biotin derivatives include, but are not limitedby, desthiobiotin, biotin alkyne or biotin azide. In some instances, abiotin described herein is desthiobiotin. In some cases, a biotindescribed herein is d-Desthiobiotin.

In some instances, the labeling group comprising biotin furthercomprises a linker. In some cases, the linker is about 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15 or more residues in length. In some instances,the linker further comprises a cleavage site, such as a proteasecleavage site (e.g., TEV cleavage site). In some cases, thebiotin-linker moiety is further isotopically-labeled, for example,isotopically labeled with ¹³C and ¹⁵N atoms at one or more amino acidresidue positions. In some cases, the biotin-linker moiety is aisotopically-labeled TEV-tag as described in Weerapana, et al.,“Quantitative reactivity profiling predicts functional cysteines inproteomes,” Nature 468(7325): 790-795.

In some cases, the labeling group comprising biotin further interactswith a streptavidin moiety. In some instances, the labeling groupcomprising biotin is further attached to a bead, such as astreptavidin-coupled bead. In some instances, the labeling groupcomprising biotin is further attached to a resin or a solid support,such as a streptavidin-coupled resin or a streptavidin-coupled solidsupport. In some instances, the solid support is a plate, a platform, acover slide, a microfluidic channel, and the like.

In some cases, the method is a high-throughput method.

In some embodiments, disclosed herein also include proteins and theirrespective binding sites identified for interaction with one or moresmall molecule ligands. In some instances, the binding sites aredisclosed in Tables 1-3. In some cases, the binding sites are disclosedin Table 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ACP1 protein, wherein the small molecule ligand binds toone or more of the following residues: VDSAATSGYEIGNPPDYR (SEQ ID NO: 1)of the ACP1 protein having the UniProtKB accession number P24666. Insome instances, also disclosed herein is a small molecule ligand whichbinds to the ACP1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:VDSAATSGYEIGNPPDYR (SEQ ID NO: 1) of the ACP1 protein having theUniProtKB accession number P24666. In some instances, the small moleculeligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ADCK3 protein, wherein the small molecule ligand binds toone or more of the following residues: LGQMLSIQDDAFINPHLAK (SEQ ID NO:2) of the ADCK3 protein having the UniProtKB accession number Q8NI60. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the ADCK3 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:LGQMLSIQDDAFINPHLAK (SEQ ID NO: 2) of the ADCK3 protein having theUniProtKB accession number Q8NI60. In some instances, the small moleculeligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ADK protein, wherein the small molecule ligand binds to oneor more of the following residues: IFTLNLSAPFISQFYK (SEQ ID NO: 3) ofthe ADK protein having the UniProtKB accession number P55263. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the ADK protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: IFTLNLSAPFISQFYK(SEQ ID NO: 3) of the ADK protein having the UniProtKB accession numberP55263. In some instances, the small molecule ligand is probe 2.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ADSS protein, wherein the small molecule ligand binds toone or more of the following residues: FIEDELQIPVK (SEQ ID NO: 4) of theADSS protein having the UniProtKB accession number P30520. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the ADSS protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: FIEDELQIPVK (SEQID NO: 4) of the ADSS protein having the UniProtKB accession numberP30520. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the AIFM1 protein, wherein the small molecule ligand binds toone or more of the following residues:PYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAK (SEQ ID NO: 5) of the AIFM1 proteinhaving the UniProtKB accession number 095831. In some embodiments, alsodisclosed herein is a small molecule ligand which binds to the AIFM1protein, wherein the small molecule ligand binds a ligand binding sitedefined by the following residues: PYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAK(SEQ ID NO: 5) of the AIFM1 protein having the UniProtKB accessionnumber 095831. In some instances, the small molecule ligand is probe 2,3, 4 or 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ALDH7A1 protein, wherein the small molecule ligand binds toone or more of the following residues: ILVEGVGEVQEYVDICDYAVGLSR (SEQ IDNO: 6) of the ALDH7A1 protein having the UniProtKB accession numberP49419. In some embodiments, also disclosed herein is a small moleculeligand which binds to the ALDH7A1 protein, wherein the small moleculeligand binds a ligand binding site defined by the following residues:ILVEGVGEVQEYVDICDYAVGLSR (SEQ ID NO: 6) of the ALDH7A1 protein havingthe UniProtKB accession number P49419. In some instances, the smallmolecule ligand is probe 8 or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to a protein selected from ARF4 or ARF5, wherein the smallmolecule ligand binds to one or more of the following residues:LGEIVTTIPTIGFNVETVEYK (SEQ ID NO: 7), corresponding toLGEIVTTIPTIGFNVETVEYK (SEQ ID NO: 7) of the ARF4 protein having theUniProtKB accession number P18085. In some embodiments, also disclosedherein is a small molecule ligand which binds to a protein selected fromARF4 or ARF5, wherein the small molecule ligand binds a ligand bindingsite defined by the following residues: LGEIVTTIPTIGFNVETVEYK (SEQ IDNO: 7), corresponding to LGEIVTTIPTIGFNVETVEYK (SEQ ID NO: 7) of theARF4 protein having the UniProtKB accession number P18085. In someinstances, the small molecule ligand is probe 2, 3, 4, 8 or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ARL1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:GTGLDEAMEWLVETLK (SEQ ID NO: 9) and LQVGEVVTTIPTIGFNVETVTYK (SEQ ID NO:10) of the ARL1 protein having the UniProtKB accession number P40616. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the ARL1 protein, wherein the small molecule ligand binds aligand binding site defined by: GTGLDEAMEWLVETLK (SEQ ID NO: 9) orLQVGEVVTTIPTIGFNVETVTYK (SEQ ID NO: 10) of the ARL1 protein having theUniProtKB accession number P40616. In some instances, the small moleculeligand is probe 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ATIC protein, wherein the small molecule ligand binds toone or more of the following residues: AFTHTAQYDEAISDYFR (SEQ ID NO: 11)of the ATIC protein having the UniProtKB accession number P31939. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the ATIC protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: AFTHTAQYDEAISDYFR(SEQ ID NO: 11) of the ATIC protein having the UniProtKB accessionnumber P31939. In some instances, the small molecule ligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the BLMH protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:CYFFLSAFVDTAQR (SEQ ID NO: 12) and GEISATQDVMMEEIFR (SEQ ID NO: 13) ofthe BLMH protein having the UniProtKB accession number Q13867. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the BLMH protein, wherein the small molecule ligand binds aligand binding site defined by: CYFFLSAFVDTAQR (SEQ ID NO: 12) orGEISATQDVMMEEIFR (SEQ ID NO: 13) of the BLMH protein having theUniProtKB accession number Q13867. In some instances, the small moleculeligand is probe 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CALR protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:SGTIFDNFLITNDEAYAEEFGNETWGVTK (SEQ ID NO: 14) and HEQNIDCGGGYVK (SEQ IDNO: 15) of the CALR protein having the UniProtKB accession numberP27797. In some embodiments, also disclosed herein is a small moleculeligand which binds to the CALR protein, wherein the small moleculeligand binds a ligand binding site defined by:SGTIFDNFLITNDEAYAEEFGNETWGVTK (SEQ ID NO: 14) or HEQNIDCGGGYVK (SEQ IDNO: 15) of the CALR protein having the UniProtKB accession numberP27797. In some instances, the small molecule ligand is probe 6, 9, or13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CAPN1 protein, wherein the small molecule ligand binds toone or more of the following residues: LVFVHSAEGNEFWSALLEK (SEQ ID NO:16) of the CAPN1 protein having the UniProtKB accession number P07384.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the CAPN1 protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:LVFVHSAEGNEFWSALLEK (SEQ ID NO: 16) of the CAPN1 protein having theUniProtKB accession number P07384. In some instances, the small moleculeligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CKB protein, wherein the small molecule ligand binds to oneor more residues of a ligand binding site selected from:FPAEDEFPDLSAHNNHMAK (SEQ ID NO: 17), LAVEALSSLDGDLAGR (SEQ ID NO: 18),TFLVWVNEEDHLR (SEQ ID NO: 19), FCTGLTQIETLFK (SEQ ID NO: 20),LGFSEVELVQMVVDGVK (SEQ ID NO: 21) and LEQGQAIDDLMPAQK (SEQ ID NO: 22) ofthe CKB protein having the UniProtKB accession number P12277. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the CKB protein, wherein the small molecule ligand binds aligand binding site defined by: FPAEDEFPDLSAHNNHMAK (SEQ ID NO: 17),LAVEALSSLDGDLAGR (SEQ ID NO: 18), TFLVWVNEEDHLR (SEQ ID NO: 19),FCTGLTQIETLFK (SEQ ID NO: 20), LGFSEVELVQMVVDGVK (SEQ ID NO: 21) orLEQGQAIDDLMPAQK (SEQ ID NO: 22) of the CKB protein having the UniProtKBaccession number P12277. In some instances, the small molecule ligand isprobe 3 or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CKMT1B protein, wherein the small molecule ligand binds toone or more of the following residues: SFLIWVNEEDHTR (SEQ ID NO: 23) ofthe CKMT1B protein having the UniProtKB accession number P12532. In someembodiments, disclosed herein is a small molecule ligand which binds tothe CKMT1B protein, wherein the small molecule ligand binds a ligandbinding site defined by the following residues: SFLIWVNEEDHTR (SEQ IDNO: 23) of the CKMT1B protein having the UniProtKB accession numberP12532. In some instances, the small molecule ligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CLPP protein, wherein the small molecule ligand binds toone or more of the following residues: QSLQVIESAMER (SEQ ID NO: 24) ofthe CLPP protein having the UniProtKB accession number Q16740. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the CLPP protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: QSLQVIESAMER (SEQID NO: 24) of the CLPP protein having the UniProtKB accession numberQ16740. In some instances, the small molecule ligand is probe 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CSNK1A1 protein, wherein the small molecule ligand binds toone or more of the following residues: DYNVLVMDLLGPSLEDLFNFCSR (SEQ IDNO: 25) of the CSNK1A1 protein having the UniProtKB accession numberP48729. In some embodiments, also disclosed herein is a small moleculeligand which binds to the CSNK1A1 protein, wherein the small moleculeligand binds a ligand binding site defined by the following residues:DYNVLVMDLLGPSLEDLFNFCSR (SEQ ID NO: 25) of the CSNK1A1 protein havingthe UniProtKB accession number P48729. In some instances, the smallmolecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CSNK2B protein, wherein the small molecule ligand binds toone or more of the following residues: VYCENQPMLPIGLSDIPGEAMVK (SEQ IDNO: 26) of the CSNK2B protein having the UniProtKB accession numberP67870. In some embodiments, also disclosed herein is a small moleculeligand which binds to the CSNK2B protein, wherein the small moleculeligand binds a ligand binding site defined by the following residues:VYCENQPMLPIGLSDIPGEAMVK (SEQ ID NO: 26) of the CSNK2B protein having theUniProtKB accession number P67870. In some instances, the small moleculeligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CTSB protein, wherein the small molecule ligand binds toone or more of the following residues: GQDHCGIESEVVAGIPR (SEQ ID NO: 27)of the CTSB protein having the UniProtKB accession number P07858. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the CTSB protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: GQDHCGIESEVVAGIPR(SEQ ID NO: 27) of the CTSB protein having the UniProtKB accessionnumber P07858. In some cases, the small molecule ligand is probe 2, 4, 9or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CTSD protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:DPDAQPGGELMLGGTDSK (SEQ ID NO: 28), EGCEAIVDTGTSLMVGPVDEVR (SEQ ID NO:29) and AIGAVPLIQGEYMIPCEK (SEQ ID NO: 30) of the CTSD protein havingthe UniProtKB accession number P07339. In some embodiments, alsodisclosed herein is a small molecule ligand which binds to the CTSDprotein, wherein the small molecule ligand binds a ligand binding sitedefined by: DPDAQPGGELMLGGTDSK (SEQ ID NO: 28), EGCEAIVDTGTSLMVGPVDEVR(SEQ ID NO: 29) or AIGAVPLIQGEYMIPCEK (SEQ ID NO: 30) of the CTSDprotein having the UniProtKB accession number P07339. In some cases, thesmall molecule ligand is probe 2, 3, 4, 6, 8, 9, 13, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the CYB5R3 protein, wherein the small molecule ligand binds toone or more of the following residues: LWYTLDR (SEQ ID NO: 31) of theCYB5R3 protein having the UniProtKB accession number P00387. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the CYB5R3 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: LWYTLDR (SEQ IDNO: 31) of the CYB5R3 protein having the UniProtKB accession numberP00387. In some cases, the small molecule ligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the DECR1 protein, wherein the small molecule ligand binds toone or more of the following residues: FDGGEEVLISGEFNDLR (SEQ ID NO: 32)of the DECR1 protein having the UniProtKB accession number Q16698. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the DECR1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: FDGGEEVLISGEFNDLR(SEQ ID NO: 32) of the DECR1 protein having the UniProtKB accessionnumber Q16698. In some cases, the small molecule ligand is probe 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the DHX9 protein, wherein the small molecule ligand binds toone or more of the following residues: ISAVSVAER (SEQ ID NO: 33) of theDHX9 protein having the UniProtKB accession number Q08211. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the DHX9 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: ISAVSVAER (SEQ IDNO: 33) of the DHX9 protein having the UniProtKB accession numberQ08211. In some cases, the small molecule ligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the DLD protein, wherein the small molecule ligand binds to oneor more of the following residues: VLGAHILGPGAGEMVNEAALALEYGASCEDIAR(SEQ ID NO: 34) of the DLD protein having the UniProtKB accession numberP09622. In some embodiments, also disclosed herein is a small moleculeligand which binds to the DLD protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:VLGAHILGPGAGEMVNEAALALEYGASCEDIAR (SEQ ID NO: 34) of the DLD proteinhaving the UniProtKB accession number P09622. In some cases, the smallmolecule ligand is probe 4, 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ECH1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:MFTAGIDLMDMASDILQPK (SEQ ID NO: 35), YQETFNVIER (SEQ ID NO: 36) andEVDVGLAADVGTLQR (SEQ ID NO: 37) of the ECH1 protein having the UniProtKBaccession number Q13011. In some embodiments, also disclosed herein is asmall molecule ligand which binds to the ECH1 protein, wherein the smallmolecule ligand binds a ligand binding site defined by:MFTAGIDLMDMASDILQPK (SEQ ID NO: 35), YQETFNVIER (SEQ ID NO: 36) orEVDVGLAADVGTLQR (SEQ ID NO: 37) of the ECH1 protein having the UniProtKBaccession number Q13011. In some cases, the small molecule ligand isprobe 3, 4, 6, 8, 13, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the EIF4A1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:MFVLDEADEMLSR (SEQ ID NO: 38) and GYDVIAQAQSGTGK (SEQ ID NO: 39) of theEIF4A1 protein having the UniProtKB accession number P60842. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the EIF4A1 protein, wherein the small molecule ligand binds aligand binding site defined by: MFVLDEADEMLSR (SEQ ID NO: 38) orGYDVIAQAQSGTGK (SEQ ID NO: 39) of the EIF4A1 protein having theUniProtKB accession number P60842. In some cases, the small moleculeligand is probe 9, 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the EIF4A2 protein, wherein the small molecule ligand binds toone or more of the following residues: GYDVIAQAQSGTGK (SEQ ID NO: 40) ofthe EIF4A2 protein having the UniProtKB accession number Q14240. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the EIF4A2 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: GYDVIAQAQSGTGK(SEQ ID NO: 40) of the EIF4A2 protein having the UniProtKB accessionnumber Q14240. In some instances, the small molecule ligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the ETFB protein, wherein the small molecule ligand binds toone or more of the following residues: HSMNPFCEIAVEEAVR (SEQ ID NO: 41)of the ETFB protein having the UniProtKB accession number P38117. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the ETFB protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: HSMNPFCEIAVEEAVR(SEQ ID NO: 41) of the ETFB protein having the UniProtKB accessionnumber P38117. In some cases, the small molecule ligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the FECH protein, wherein the small molecule ligand binds toone or more of the following residues: SEVVILFSAHSLPMSVVNR (SEQ ID NO:42) of the FECH protein having the UniProtKB accession number P22830. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the FECH protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:SEVVILFSAHSLPMSVVNR (SEQ ID NO: 42) of the FECH protein having theUniProtKB accession number P22830. In some cases, the small moleculeligand is probe 4.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GLA protein, wherein the small molecule ligand binds to oneor more residues of a ligand binding site selected from: SILDWTSFNQER(SEQ ID NO: 43), FMCNLDCQEEPDSCISEK (SEQ ID NO: 44) and LFMEMAELMVSEGWK(SEQ ID NO: 45) of the GLA protein having the UniProtKB accession numberP06280. In some embodiments, also disclosed herein is a small moleculeligand which binds to the GLA protein, wherein the small molecule ligandbinds a ligand binding site defined by: SILDWTSFNQER (SEQ ID NO: 43),FMCNLDCQEEPDSCISEK (SEQ ID NO: 44) or LFMEMAELMVSEGWK (SEQ ID NO: 45) ofthe GLA protein having the UniProtKB accession number P06280. In somecases, the small molecule ligand is probe 4 or 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GLB1 protein, wherein the small molecule ligand binds toone or more of the following residues: TEAVASSLYDILAR (SEQ ID NO: 46) ofthe GLB1 protein having the UniProtKB accession number P16278. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the GLB1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: TEAVASSLYDILAR(SEQ ID NO: 46) of the GLB1 protein having the UniProtKB accessionnumber P16278. In some instances, the small molecule ligand is probe 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GLO1 protein, wherein the small molecule ligand binds toone or more of the following residues: GLAFIQDPDGYWIEILNPNK (SEQ ID NO:47) of the GLO1 protein having the UniProtKB accession number Q04760. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the GLO1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:GLAFIQDPDGYWIEILNPNK (SEQ ID NO: 47) of the GLO1 protein having theUniProtKB accession number Q04760. In some instances, the small moleculeligand is probe 3 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GLUD1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from: YSTDVSVDEVK(SEQ ID NO: 48) and HGGTIPIVPTAEFQDR (SEQ ID NO: 49) of the GLUD1protein having the UniProtKB accession number P00367. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the GLUD1 protein, wherein the small molecule ligand binds aligand binding site defined by: YSTDVSVDEVK (SEQ ID NO: 48) orHGGTIPIVPTAEFQDR (SEQ ID NO: 49) of the GLUD1 protein having theUniProtKB accession number P00367. In some instances, the small moleculeligand is probe 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GOLPH3 protein, wherein the small molecule ligand binds toone or more of the following residues: EGYTSFWNDCISSGLR (SEQ ID NO: 50)of the GOLPH3 protein having the UniProtKB accession number Q9H4A6. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the GOLPH3 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: EGYTSFWNDCISSGLR(SEQ ID NO: 50) of the GOLPH3 protein having the UniProtKB accessionnumber Q9H4A6. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the GSTP1 protein, wherein the small molecule ligand binds toone or more of the following residues: FQDGDLTLYQSNTILR (SEQ ID NO: 51)of the GSTP1 protein having the UniProtKB accession number P09211. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the GSTP1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: FQDGDLTLYQSNTILR(SEQ ID NO: 51) of the GSTP1 protein having the UniProtKB accessionnumber P09211. In some instances, the small molecule ligand is probe 2.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HBA2 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:VGAHAGEYGAEALER (SEQ ID NO: 52) and VDPVNFK (SEQ ID NO: 53) of the HBA2protein having the UniProtKB accession number P69905. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the HBA2 protein, wherein the small molecule ligand binds aligand binding site defined by: VGAHAGEYGAEALER (SEQ ID NO: 52) orVDPVNFK (SEQ ID NO: 53) of the HBA2 protein having the UniProtKBaccession number P69905. In some instances, the small molecule ligand isprobe 4.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HEXA protein, wherein the small molecule ligand binds toone or more of the following residues: LTSDLTFAYER (SEQ ID NO: 54) ofthe HEXA protein having the UniProtKB accession number P06865. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the HEXA protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: LTSDLTFAYER (SEQID NO: 54) of the HEXA protein having the UniProtKB accession numberP06865. In some instances, the small molecule ligand is probe 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HMOX2 protein, wherein the small molecule ligand binds toone or more of the following residues: AENTQFVK (SEQ ID NO: 55) andLATTALYFTYSALEEEMER (SEQ ID NO: 56) of the HMOX2 protein having theUniProtKB accession number P30519. In some embodiments, also disclosedherein is a small molecule ligand which binds to the HMOX2 protein,wherein the small molecule ligand binds a ligand binding site defined bythe following residues: AENTQFVK (SEQ ID NO: 55) or LATTALYFTYSALEEEMER(SEQ ID NO: 56) of the HMOX2 protein having the UniProtKB accessionnumber P30519. In some instances, the small molecule ligand is probe 2,3, 4, 6, 8, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HSD17B4 protein, wherein the small molecule ligand binds toone or more of the following residues: LGLLGLANSLAIEGR (SEQ ID NO: 57)of the HSD17B4 protein having the UniProtKB accession number P51659. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the HSD17B4 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: LGLLGLANSLAIEGR(SEQ ID NO: 57) of the HSD17B4 protein having the UniProtKB accessionnumber P51659. In some instances, the small molecule ligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HSP90AB1 protein, wherein the small molecule ligand bindsto one or more residues of a ligand binding site selected from:VFIMDSCDELIPEYLNFIR (SEQ ID NO: 58) and GFEVVYMTEPIDEYCVQQLK (SEQ ID NO:59) of the HSP90AB1 protein having the UniProtKB accession numberP08238. In some embodiments, also disclosed herein is a small moleculeligand which binds to the HSP90AB1 protein, wherein the small moleculeligand binds a ligand binding site defined by: VFIMDSCDELIPEYLNFIR (SEQID NO: 58) or GFEVVYMTEPIDEYCVQQLK (SEQ ID NO: 59) of the HSP90AB1protein having the UniProtKB accession number P08238. In some instances,the small molecule ligand is probe 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HSP90B1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:LISLTDENALSGNEELTVK (SEQ ID NO: 60) and YSQFINFPIYVWSSK (SEQ ID NO: 61)of the HSP90B1 protein having the UniProtKB accession number P14625. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the HSP90B1 protein, wherein the small molecule ligand binds aligand binding site defined by: LISLTDENALSGNEELTVK (SEQ ID NO: 60) orYSQFINFPIYVWSSK (SEQ ID NO: 61) of the HSP90B1 protein having theUniProtKB accession number P14625. In some instances, the small moleculeligand is probe 6 or 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the HSPA8 protein, wherein the small molecule ligand binds toone or more of the following residues: SFYPEEVSSMVLTK (SEQ ID NO: 62) ofthe HSPA8 protein having the UniProtKB accession number P11142. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the HSPA8 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: SFYPEEVSSMVLTK(SEQ ID NO: 62) of the HSPA8 protein having the UniProtKB accessionnumber P11142. In some instances, the small molecule ligand is probe 13or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the IMPDH2 protein, wherein the small molecule ligand binds toone or more of the following residues: YEQGFITDPVVLSPK (SEQ ID NO: 63)of the IMPDH2 protein having the UniProtKB accession number P12268. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the IMPDH2 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: YEQGFITDPVVLSPK(SEQ ID NO: 63) of the IMPDH2 protein having the UniProtKB accessionnumber P12268. In some instances, the small molecule ligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the LDHA protein, wherein the small molecule ligand binds toone or more of the following residues: DLADELALVDVIEDK (SEQ ID NO: 64)of the LDHA protein having the UniProtKB accession number P00338. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the LDHA protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: DLADELALVDVIEDK(SEQ ID NO: 64) of the LDHA protein having the UniProtKB accessionnumber P00338. In some instances, the small molecule ligand is probe 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the LDHB protein, wherein the small molecule ligand binds toone or more of the following residues: MVVESAYEVIK (SEQ ID NO: 65) ofthe LDHB protein having the UniProtKB accession number P07195. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the LDHB protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: MVVESAYEVIK (SEQID NO: 65) of the LDHB protein having the UniProtKB accession numberP07195. In some instances, the small molecule ligand is probe 4.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the LGMN protein, wherein the small molecule ligand binds toone or more of the following residues: DYTGEDVTPQNFLAVLR (SEQ ID NO: 66)of the LGMN protein having the UniProtKB accession number Q99538. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the LGMN protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: DYTGEDVTPQNFLAVLR(SEQ ID NO: 66) of the LGMN protein having the UniProtKB accessionnumber Q99538. In some instances, the small molecule ligand is probe 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the LTA4H protein, wherein the small molecule ligand binds toone or more of the following residues: LVVDLTDIDPDVAYSSVPYEK (SEQ ID NO:67) of the LTA4H protein having the UniProtKB accession number P09960.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the LTA4H protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:LVVDLTDIDPDVAYSSVPYEK (SEQ ID NO: 67) of the LTA4H protein having theUniProtKB accession number P09960. In some cases, the small moleculeligand is probe 4, 8 or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the NAMPT protein, wherein the small molecule ligand binds toone or more of the following residues: YLLETSGNLDGLEYK (SEQ ID NO: 68)of the NAMPT protein having the UniProtKB accession number P43490. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the NAMPT protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: YLLETSGNLDGLEYK(SEQ ID NO: 68) of the NAMPT protein having the UniProtKB accessionnumber P43490. In some cases, the small molecule ligand is probe 3, 6,8, 13, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the NPM1 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from:DELHIVEAEAMNYEGSPIK (SEQ ID NO: 69) and MSVQPTVSLGGFEITPPVVLR (SEQ IDNO: 70) of the NPM1 protein having the UniProtKB accession numberP06748. In some embodiments, also disclosed herein is a small moleculeligand which binds to the NPM1 protein, wherein the small moleculeligand binds a ligand binding site defined by: DELHIVEAEAMNYEGSPIK (SEQID NO: 69) or MSVQPTVSLGGFEITPPVVLR (SEQ ID NO: 70) of the NPM1 proteinhaving the UniProtKB accession number P06748. In some cases, the smallmolecule ligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PCMT1 protein, wherein the small molecule ligand binds toone or more of the following residues: LILPVGPAGGNQMLEQYDK (SEQ ID NO:71) of the PCMT1 protein having the UniProtKB accession number P22061.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the PCMT1 protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:LILPVGPAGGNQMLEQYDK (SEQ ID NO: 71) of the PCMT1 protein having theUniProtKB accession number P22061. In some instances, the small moleculeligand is probe 2, 3 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PDHB protein, wherein the small molecule ligand binds toone or more of the following residues: VFLLGEEVAQYDGAYK (SEQ ID NO: 72)of the PDHB protein having the UniProtKB accession number P11177. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the PDHB protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: VFLLGEEVAQYDGAYK(SEQ ID NO: 72) of the PDHB protein having the UniProtKB accessionnumber P11177. In some instances, the small molecule ligand is probe 2,3, 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PGK1 protein, wherein the small molecule ligand binds toone or more of the following residues: QIVWNGPVGVFEWEAFAR (SEQ ID NO:73) of the PGK1 protein having the UniProtKB accession number P00558. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the PGK1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:QIVWNGPVGVFEWEAFAR (SEQ ID NO: 73) of the PGK1 protein having theUniProtKB accession number P00558. In some instances, the small moleculeligand is probe 3.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PKM protein, wherein the small molecule ligand binds to oneor more of the following residues: IYVDDGLISLQVK (SEQ ID NO: 74) andLAPITSDPTEATAVGAVEASFK (SEQ ID NO: 75) of the PKM protein having theUniProtKB accession number P14618. In some embodiments, also disclosedherein is a small molecule ligand which binds to the PKM protein,wherein the small molecule ligand binds a ligand binding site defined bythe following residues: IYVDDGLISLQVK (SEQ ID NO: 74) orLAPITSDPTEATAVGAVEASFK (SEQ ID NO: 75) of the PKM protein having theUniProtKB accession number P14618. In some instances, the small moleculeligand is probe 2 or 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the POR protein, wherein the small molecule ligand binds to oneor more of the following residues: TALTYYLDITNPPR (SEQ ID NO: 76) of thePOR protein having the UniProtKB accession number P16435. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the POR protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: TALTYYLDITNPPR(SEQ ID NO: 76) of the POR protein having the UniProtKB accession numberP16435. In some instances, the small molecule ligand is probe 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to a protein selected from PPP1CA and PPP1CC, wherein the smallmolecule ligand binds to one or more of the following residues:IYGFYDECK (SEQ ID NO: 77), which corresponds to IYGFYDECK (SEQ ID NO:78) of the PPP1CC protein having the UniProtKB accession number P36873.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to a protein selected from PPP1CA and PPP1CC, wherein thesmall molecule ligand binds a ligand binding site defined by thefollowing residues: IYGFYDECK (SEQ ID NO: 77), which corresponds toIYGFYDECK (SEQ ID NO: 78) of the PPP1CC protein having the UniProtKBaccession number P36873. In some instances, the small molecule ligand isprobe 2.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PPP1CC protein, wherein the small molecule ligand binds toone or more of the following residues: EIFLSQPILLELEAPLK (SEQ ID NO: 79)of the PPP1CC protein having the UniProtKB accession number P36873. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the PPP1CC protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: EIFLSQPILLELEAPLK(SEQ ID NO: 79) of the PPP1CC protein having the UniProtKB accessionnumber P36873. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PPT1 protein, wherein the small molecule ligand binds toone or more of the following residues: TLMEDVENSFFLNVNSQVTTVCQALAK (SEQID NO: 80) of the PPT1 protein having the UniProtKB accession numberP50897. In some embodiments, also disclosed herein is a small moleculeligand which binds to the PPT1 protein, wherein the small moleculeligand binds a ligand binding site defined by the following residues:TLMEDVENSFFLNVNSQVTTVCQALAK (SEQ ID NO: 80) of the PPT1 protein havingthe UniProtKB accession number P50897. In some cases, the small moleculeligand is probe 2, 4, 8, 9, 13, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PRDX2 protein, wherein the small molecule ligand binds toone or more of the following residues: TDEGIAYR (SEQ ID NO: 81) of thePRDX2 protein having the UniProtKB accession number P32119. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the PRDX2 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: TDEGIAYR (SEQ IDNO: 81) of the PRDX2 protein having the UniProtKB accession numberP32119. In some cases, the small molecule ligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PSMB4 protein, wherein the small molecule ligand binds toone or more of the following residues: FEGGVVIAADMLGSYGSLAR (SEQ ID NO:82) of the PSMB4 protein having the UniProtKB accession number P28070.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the PSMB4 protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:FEGGVVIAADMLGSYGSLAR (SEQ ID NO: 82) of the PSMB4 protein having theUniProtKB accession number P28070. In some cases, the small moleculeligand is probe 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PSMB5 protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from: LLANMVYQYK(SEQ ID NO: 83) and DAYSGGAVNLYHVR (SEQ ID NO: 84) of the PSMB5 proteinhaving the UniProtKB accession number P28074. In some embodiments, alsodisclosed herein is a small molecule ligand which binds to the PSMB5protein, wherein the small molecule ligand binds a ligand binding sitedefined by: LLANMVYQYK (SEQ ID NO: 83) or DAYSGGAVNLYHVR (SEQ ID NO: 84)of the PSMB5 protein having the UniProtKB accession number P28074. Insome instances, the small molecule ligand is probe 3, 4 or 6.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the PSMB6 protein, wherein the small molecule ligand binds toone or more of the following residues:SGSAADTQAVADAVTYQLGFHSIELNEPPLVHTAASLFK (SEQ ID NO: 85) of the PSMB6protein having the UniProtKB accession number P28072. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the PSMB6 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:SGSAADTQAVADAVTYQLGFHSIELNEPPLVHTAASLFK (SEQ ID NO: 85) of the PSMB6protein having the UniProtKB accession number P28072. In some instances,the small molecule ligand is probe 3, 6 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the RAB7A protein, wherein the small molecule ligand binds toone or more of the following residues: DEFLIQASPR (SEQ ID NO: 86) of theRAB7A protein having the UniProtKB accession number P51149. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the RAB7A protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: DEFLIQASPR (SEQID NO: 86) of the RAB7A protein having the UniProtKB accession numberP51149. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the RUVBL2 protein, wherein the small molecule ligand binds toone or more of the following residues: ALESDMAPVLIMATNR (SEQ ID NO: 87)of the RUVBL2 protein having the UniProtKB accession number Q9Y230. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the RUVBL2 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: ALESDMAPVLIMATNR(SEQ ID NO: 87) of the RUVBL2 protein having the UniProtKB accessionnumber Q9Y230. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the SMYD3 protein, wherein the small molecule ligand binds toone or more of the following residues: DQYCFECDCFR (SEQ ID NO: 88) ofthe SMYD3 protein having the UniProtKB accession number Q9H7B4. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the SMYD3 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: DQYCFECDCFR (SEQID NO: 88) of the SMYD3 protein having the UniProtKB accession numberQ9H7B4. In some cases, the small molecule ligand is probe 9.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the TPP1 protein, wherein the small molecule ligand binds toone or more of the following residues:GCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLK (SEQ ID NO: 89) of the TPP1protein having the UniProtKB accession number 014773. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the TPP1 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues:GCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLK (SEQ ID NO: 89) of the TPP1protein having the UniProtKB accession number 014773. In some instances,the small molecule ligand is probe 4, 9, 13, 14 or 15.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the TXNDC17 protein, wherein the small molecule ligand binds toone or more of the following residues: YEEVSVSGFEEFHR (SEQ ID NO: 90) ofthe TXNDC17 protein having the UniProtKB accession number Q9BRA2. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the TXNDC17 protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: YEEVSVSGFEEFHR(SEQ ID NO: 90) of the TXNDC17 protein having the UniProtKB accessionnumber Q9BRA2. In some instances, the small molecule ligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the YWHAE protein, wherein the small molecule ligand binds toone or more residues of a ligand binding site selected from: EAAENSLVAYK(SEQ ID NO: 91) and AAFDDAIAELDTLSEESYK (SEQ ID NO: 92) of the YWHAEprotein having the UniProtKB accession number P62258. In someembodiments, also disclosed herein is a small molecule ligand whichbinds to the YWHAE protein, wherein the small molecule ligand binds aligand binding site defined by: EAAENSLVAYK (SEQ ID NO: 91) orAAFDDAIAELDTLSEESYK (SEQ ID NO: 92) of the YWHAE protein having theUniProtKB accession number P62258. In some cases, the small moleculeligand is probe 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the YWHAQ protein, wherein the small molecule ligand binds toone or more of the following residues: TAFDEAIAELDTLNEDSYK (SEQ ID NO:93) of the YWHAQ protein having the UniProtKB accession number P27348.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the YWHAQ protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:TAFDEAIAELDTLNEDSYK (SEQ ID NO: 93) of the YWHAQ protein having theUniProtKB accession number P27348. In some cases, the small moleculeligand is probe 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the YWHAZ protein, wherein the small molecule ligand binds toone or more of the following residues: TAFDEAIAELDTLSEESYK (SEQ ID NO:94) of the YWHAZ protein having the UniProtKB accession number P63104.In some embodiments, also disclosed herein is a small molecule ligandwhich binds to the YWHAZ protein, wherein the small molecule ligandbinds a ligand binding site defined by the following residues:TAFDEAIAELDTLSEESYK (SEQ ID NO: 94) of the YWHAZ protein having theUniProtKB accession number P63104. In some instances, the small moleculeligand is probe 13 or 14.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the EXO1 protein, wherein the small molecule ligand binds toone or more of the following residues: SQGVDCLVAPYEADAQLAYLNK (SEQ IDNO: 95) of the EXO1 protein having the UniProtKB accession numberQ9UQ84. In some embodiments, also disclosed herein is a small moleculeligand which binds to the EXO1 protein, wherein the small moleculeligand binds a ligand binding site defined by the following residues:SQGVDCLVAPYEADAQLAYLNK (SEQ ID NO: 95) of the EXO1 protein having theUniProtKB accession number Q9UQ84. In some instances, the small moleculeligand is probe 2, 6, 8, 9 or 13.

In some embodiments, disclosed herein is a small molecule ligand whichbinds to the LMNA protein, wherein the small molecule ligand binds toone or more of the following residues: MQQQLDEYQELLDIK (SEQ ID NO: 96)of the LMNA protein having the UniProtKB accession number P02545. Insome embodiments, also disclosed herein is a small molecule ligand whichbinds to the LMNA protein, wherein the small molecule ligand binds aligand binding site defined by the following residues: MQQQLDEYQELLDIK(SEQ ID NO: 96) of the LMNA protein having the UniProtKB accessionnumber P02545. In some instances, the small molecule ligand is probe 6or 13.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (Ia):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring wherein R¹is hydrogen and R² is selected from substituted alkyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted cycloalkyl, optionally substituted heterocyclyl, optionallysubstituted heteroaryl, optionally substituted aralkyl, optionallysubstituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring; and R³ isan optionally substituted C2-C6 alkyl.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (IIa):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring; and R³ isan optionally substituted C2-C6 alkyl.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (IIIa):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring; and R³ isan optionally substituted C2-C6 alkyl.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (IVa):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring; and R³ isan optionally substituted C2-C6 alkyl.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (Va):

wherein R¹ is selected from substituted alkyl, optionally substitutedaryl, optionally substituted heteroaryl, optionally substitutedcycloalkyl, optionally substituted heterocyclyl, optionally substitutedheteroaryl, optionally substituted aralkyl, optionally substitutedheteroarylalkyl, or optionally substituted heterocyclylalkyl; and R² isan optionally substituted C2-C6 alkyl.

In some cases, the small molecule ligand which binds to a protein has astructure represented by Formula (VIa):

wherein R¹ is hydrogen and R² is selected from substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted cycloalkyl, optionally substituted heterocyclyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroarylalkyl, or optionally substitutedheterocyclylalkyl; or R¹ and R² together with the nitrogen to which theyare attached form an optionally substituted heterocyclyl ring; and R³ isan optionally substituted C2-C6 alkyl.Cells, Analytical Techniques, and Instrumentation

In certain embodiments, one or more of the methods disclosed hereincomprise a cell sample. In some embodiments, the cell sample for usewith the methods described herein is obtained from cells of an animal.In some instances, the animal cell includes a cell from a marineinvertebrate, fish, insects, amphibian, reptile, or mammal. In someinstances, the mammalian cell is a primate, ape, equine, bovine,porcine, canine, feline, or rodent. In some instances, the mammal is aprimate, ape, dog, cat, rabbit, ferret, or the like. In some cases, therodent is a mouse, rat, hamster, gerbil, hamster, chinchilla, or guineapig. In some embodiments, the bird cell is from a canary, parakeet orparrots. In some embodiments, the reptile cell is from a turtles, lizardor snake. In some cases, the fish cell is from a tropical fish. In somecases, the fish cell is from a zebrafish (e.g. Danino rerio). In somecases, the worm cell is from a nematode (e.g. C. elegans). In somecases, the amphibian cell is from a frog. In some embodiments, thearthropod cell is from a tarantula or hermit crab.

In some embodiments, the cell sample for use with the methods describedherein is obtained from a mammalian cell. In some instances, themammalian cell is an epithelial cell, connective tissue cell, hormonesecreting cell, a nerve cell, a skeletal muscle cell, a blood cell, oran immune system cell.

Exemplary mammalian cells include, but are not limited to, 293A cellline, 293FT cell line, 293F cells, 293 H cells, HEK 293 cells, CHO DG44cells, CHO-S cells, CHO-KI cells, Expi293F™ cells, Flp-In™ T-REx™ 293cell line, Flp-In™-293 cell line, Flp-In™-3T3 cell line, Flp-In™-BHKcell line, Flp-In™-CHO cell line, Flp-In™-CV-1 cell line, Flp-In™-Jurkatcell line, FreeStyle™ 293-F cells, FreeStyle™ CHO-S cells, GripTite™ 293MSR cell line, GS-CHO cell line, HepaRG™ cells, T-REx™ Jurkat cell line,Per.C6 cells, T-REx™-293 cell line, T-REx™-CHO cell line, T-REx™-HeLacell line, NC-HIMT cell line, and PC12 cell line.

In some instances, the cell sample for use with the methods describedherein is obtained from cells of a tumor cell line. In some instances,the sample is obtained from cells of a solid tumor cell line. In someinstances, the solid tumor cell line is a sarcoma cell line. In someinstances, the solid tumor cell line is a carcinoma cell line. In someembodiments, the sarcoma cell line is obtained from a cell line ofalveolar rhabdomyosarcoma, alveolar soft part sarcoma, ameloblastoma,angiosarcoma, chondrosarcoma, chordoma, clear cell sarcoma of softtissue, dedifferentiated liposarcoma, desmoid, desmoplastic small roundcell tumor, embryonal rhabdomyosarcoma, epithelioid fibrosarcoma,epithelioid hemangioendothelioma, epithelioid sarcoma,esthesioneuroblastoma, Ewing sarcoma, extrarenal rhabdoid tumor,extraskeletal myxoid chondrosarcoma, extraskeletal osteosarcoma,fibrosarcoma, giant cell tumor, hemangiopericytoma, infantilefibrosarcoma, inflammatory myofibroblastic tumor, Kaposi sarcoma,leiomyosarcoma of bone, liposarcoma, liposarcoma of bone, malignantfibrous histiocytoma (MFH), malignant fibrous histiocytoma (MFH) ofbone, malignant mesenchymoma, malignant peripheral nerve sheath tumor,mesenchymal chondrosarcoma, myxofibrosarcoma, myxoid liposarcoma,myxoinflammatory fibroblastic sarcoma, neoplasms with perivascularepitheioid cell differentiation, osteosarcoma, parosteal osteosarcoma,neoplasm with perivascular epitheioid cell differentiation, periostealosteosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma,PNET/extraskeletal Ewing tumor, rhabdomyosarcoma, round cellliposarcoma, small cell osteosarcoma, solitary fibrous tumor, synovialsarcoma, telangiectatic osteosarcoma.

In some embodiments, the carcinoma cell line is obtained from a cellline of adenocarcinoma, squamous cell carcinoma, adenosquamouscarcinoma, anaplastic carcinoma, large cell carcinoma, small cellcarcinoma, anal cancer, appendix cancer, bile duct cancer (i.e.,cholangiocarcinoma), bladder cancer, brain tumor, breast cancer,cervical cancer, colon cancer, cancer of Unknown Primary (CUP),esophageal cancer, eye cancer, fallopian tube cancer,gastroenterological cancer, kidney cancer, liver cancer, lung cancer,medulloblastoma, melanoma, oral cancer, ovarian cancer, pancreaticcancer, parathyroid disease, penile cancer, pituitary tumor, prostatecancer, rectal cancer, skin cancer, stomach cancer, testicular cancer,throat cancer, thyroid cancer, uterine cancer, vaginal cancer, or vulvarcancer.

In some instances, the cell sample is obtained from cells of ahematologic malignant cell line. In some instances, the hematologicmalignant cell line is a T-cell cell line. In some instances, B-cellcell line. In some instances, the hematologic malignant cell line isobtained from a T-cell cell line of: peripheral T-cell lymphoma nototherwise specified (PTCL-NOS), anaplastic large cell lymphoma,angioimmunoblastic lymphoma, cutaneous T-cell lymphoma, adult T-cellleukemia/lymphoma (ATLL), blastic NK-cell lymphoma, enteropathy-typeT-cell lymphoma, hematosplenic gamma-delta T-cell lymphoma,lymphoblastic lymphoma, nasal NK/T-cell lymphomas, or treatment-relatedT-cell lymphomas.

In some instances, the hematologic malignant cell line is obtained froma B-cell cell line of: acute lymphoblastic leukemia (ALL), acutemyelogenous leukemia (AML), chronic myelogenous leukemia (CML), acutemonocytic leukemia (AMoL), chronic lymphocytic leukemia (CLL), high-riskchronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL),high-risk small lymphocytic lymphoma (SLL), follicular lymphoma (FL),mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia, multiplemyeloma, extranodal marginal zone B cell lymphoma, nodal marginal zone Bcell lymphoma, Burkitt's lymphoma, non-Burkitt high grade B celllymphoma, primary mediastinal B-cell lymphoma (PMBL), immunoblasticlarge cell lymphoma, precursor B-lymphoblastic lymphoma, B cellprolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginalzone lymphoma, plasma cell myeloma, plasmacytoma, mediastinal (thymic)large B cell lymphoma, intravascular large B cell lymphoma, primaryeffusion lymphoma, or lymphomatoid granulomatosis.

In some embodiments, the cell sample for use with the methods describedherein is obtained from a tumor cell line. Exemplary tumor cell lineincludes, but is not limited to, 600MPE, AU565, BT-20, BT-474, BT-483,BT-549, Evsa-T, Hs578T, MCF-7, MDA-MB-231, SkBr3, T-47D, HeLa, DU145,PC3, LNCaP, A549, H1299, NCI-H460, A2780, SKOV-3/Luc, Neuro2a, RKO,RKO-AS45-1, HT-29, SW1417, SW948, DLD-1, SW480, Capan-1, MC/9, B72.3,B25.2, B6.2, B38.1, DMS 153, SU.86.86, SNU-182, SNU-423, SNU-449,SNU-475, SNU-387, Hs817.T, LMH, LMH/2A, SNU-398, PLHC-1, HepG2/SF,OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-Ly4, OCI-Ly6, OCI-Ly7, OCI-Ly10,OCI-Ly18, OCI-Ly19, U2932, DB, HBL-1, RIVA, SUDHL2, TMD8, MEC1, MEC2,8E5, CCRF-CEM, MOLT-3, TALL-104, AML-193, THP-1, BDCM, HL-60, Jurkat,RPMI 8226, MOLT-4, RS4, K-562, KASUMI-1, Daudi, GA-10, Raji, JeKo-1,NK-92, and Mino.

In some embodiments, the cell sample for use in the methods is from anytissue or fluid from an individual. Samples include, but are not limitedto, tissue (e.g. connective tissue, muscle tissue, nervous tissue, orepithelial tissue), whole blood, dissociated bone marrow, bone marrowaspirate, pleural fluid, peritoneal fluid, central spinal fluid,abdominal fluid, pancreatic fluid, cerebrospinal fluid, brain fluid,ascites, pericardial fluid, urine, saliva, bronchial lavage, sweat,tears, ear flow, sputum, hydrocele fluid, semen, vaginal flow, milk,amniotic fluid, and secretions of respiratory, intestinal orgenitourinary tract. In some embodiments, the sample is a tissue sample,such as a sample obtained from a biopsy or a tumor tissue sample. Insome embodiments, the sample is a blood serum sample. In someembodiments, the sample is a blood cell sample containing one or moreperipheral blood mononuclear cells (PBMCs). In some embodiments, thesample contains one or more circulating tumor cells (CTCs). In someembodiments, the sample contains one or more disseminated tumor cells(DTC, e.g., in a bone marrow aspirate sample).

In some embodiments, the cell samples are obtained from the individualby any suitable means of obtaining the sample using well-known androutine clinical methods. Procedures for obtaining tissue samples froman individual are well known. For example, procedures for drawing andprocessing tissue sample such as from a needle aspiration biopsy iswell-known and is employed to obtain a sample for use in the methodsprovided. Typically, for collection of such a tissue sample, a thinhollow needle is inserted into a mass such as a tumor mass for samplingof cells that, after being stained, will be examined under a microscope.

Sample Preparation and Analysis

In some embodiments, the sample is a sample solution. In some instances,the sample solution comprises a solution such as a buffer (e.g.phosphate buffered saline) or a media. In some embodiments, the media isan isotopically labeled media. In some instances, the sample solution isa cell solution.

In some embodiments, the sample (e.g., cells or a cell solution) isincubated with one or more probes for analysis of protein-probeinteractions. In some instances, the sample (e.g., cells or a cellsolution) is further incubated in the presence of an additional probeprior to addition of the one or more probes. In other instances, thesample (e.g., cells or a cell solution) is further incubated with anon-probe small molecule ligand, in which the non-probe small moleculeligand does not contain a photoreactive moiety and/or an alkyne group.In such instances, the sample is incubated with a probe and non-probesmall molecule ligand for competitive protein profiling analysis.

In some cases, the sample is compared with a control. In some cases, adifference is observed between a set of probe protein interactionsbetween the sample and the control. In some instances, the differencecorrelates to the interaction between the small molecule fragment andthe proteins.

In some embodiments, one or more methods are utilized for labeling asample (e.g. cells or a cell solution) for analysis of probe proteininteractions. In some instances, a method comprises labeling the sample(e.g. cells or a cell solution) with an enriched media. In some cases,the sample (e.g. cells or a cell solution) is labeled withisotope-labeled amino acids, such as ¹³C or ¹⁵N-labeled amino acids. Insome cases, the labeled sample is further compared with a non-labeledsample to detect differences in probe protein interactions between thetwo samples. In some instances, this difference is a difference of atarget protein and its interaction with a small molecule ligand in thelabeled sample versus the non-labeled sample. In some instances, thedifference is an increase, decrease or a lack of protein-probeinteraction in the two samples. In some instances, the isotope-labeledmethod is termed SILAC, stable isotope labeling using amino acids incell culture.

In some instances, the sample is divided into a first cell solution anda second cell solution. In some cases, the first cell solution isincubated with a first probe for an extended period of time to generatea first group of probe-protein complexes. In some instances, theextended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutesor longer. In some instances, the second cell solution comprises asecond probe to generate a second group of probe-protein complexes. Insome instances, the first probe and the second probe are different. Insome embodiments, cells from the second cell solution are treated with abuffer, such as a control buffer, in which the buffer does not contain asmall molecule fragment probe. In some embodiments, the control buffercomprises dimethyl sulfoxide (DMSO).

In some embodiments, a method comprises incubating a sample (e.g. cellsor a cell solution) or a processed sample (e.g., a cell lysate) with alabeling group (e.g., an isotopically labeled labeling group) to tag oneor more proteins of interest for further analysis. In such cases, thelabeling group comprises a biotin, a streptavidin, bead, resin, a solidsupport, or a combination thereof, and further comprises a linker thatis optionally isotopically labeled. As described above, the linker canbe about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more residues inlength and can further comprise a cleavage site, such as a proteasecleavage site (e.g., TEV cleavage site). In some cases, the labelinggroup is a biotin-linker moiety, which is optionally isotopicallylabeled with ¹³C and ¹⁵N atoms at one or more amino acid residuepositions within the linker. In some cases, the biotin-linker moiety isa isotopically-labeled TEV-tag as described in Weerapana, et al.,“Quantitative reactivity profiling predicts functional cysteines inproteomes,” Nature 468(7325): 790-795.

In some embodiments, an isotopic reductive dimethylation (ReDi) methodis utilized for processing a sample. In some cases, the ReDi labelingmethod involves reacting peptides with formaldehyde to form a Schiffbase, which is then reduced by cyanoborohydride. This reactiondimethylates free amino groups on N-termini and lysine side chains andmonomethylates N-terminal prolines. In some cases, the ReDi labelingmethod comprises methylating peptides from a first processed sample witha “light” label using reagents with hydrogen atoms in their naturalisotopic distribution and peptides from a second processed sample with a“heavy” label using deuterated formaldehyde and cyanoborohydride.Subsequent proteomic analysis (e.g., mass spectrometry analysis) basedon a relative peptide abundance between the heavy and light peptideversion can be used for analysis of probe-protein interactions.

In some embodiments, isobaric tags for relative and absolutequantitation (iTRAQ) method is utilized for processing a sample. In somecases, the iTRAQ method is based on the covalent labeling of theN-terminus and side chain amines of peptides from a processed sample. Insome cases, reagent such as 4-plex or 8-plex is used for labeling thepeptides.

In some embodiments, the probe-protein complex is further conjugated toa chromophore, such as a fluorophore. In some instances, theprobe-protein complex is separated and visualized utilizing anelectrophoresis system, such as through a gel electrophoresis, or acapillary electrophoresis. Exemplary gel electrophoresis includesagarose based gels, polyacrylamide based gels, or starch based gels. Insome instances, the probe-protein is subjected to a nativeelectrophoresis condition. In some instances, the probe-protein issubjected to a denaturing electrophoresis condition.

In some instances, the probe-protein after harvesting is furtherfragmentized to generate protein fragments. In some instances,fragmentation is generated through mechanical stress, pressure, orchemical means. In some instances, the protein from the probe-proteincomplexes is fragmented by a chemical means. In some embodiments, thechemical means is a protease. Exemplary proteases include, but are notlimited to, serine proteases such as chymotrypsin A, penicillin Gacylase precursor, dipeptidase E, DmpA aminopeptidase, subtilisin,prolyl oligopeptidase, D-Ala-D-Ala peptidase C, signal peptidase I,cytomegalovirus assemblin, Lon-A peptidase, peptidase Clp, Escherichiacoli phage KlF endosialidase CIMCD self-cleaving protein, nucleoporin145, lactoferrin, murein tetrapeptidase LD-carboxypeptidase, orrhomboid-1; threonine proteases such as ornithine acetyltransferase;cysteine proteases such as TEV protease, amidophosphoribosyltransferaseprecursor, gamma-glutamyl hydrolase (Rattus norvegicus), hedgehogprotein, DmpA aminopeptidase, papain, bromelain, cathepsin K, calpain,caspase-1, separase, adenain, pyroglutamyl-peptidase I, sortase A,hepatitis C virus peptidase 2, sindbis virus-type nsP2 peptidase,dipeptidyl-peptidase VI, or DeSI-1 peptidase; aspartate proteases suchas beta-secretase 1 (BACE1), beta-secretase 2 (BACE2), cathepsin D,cathepsin E, chymosin, napsin-A, nepenthesin, pepsin, plasmepsin,presenilin, or renin; glutamic acid proteases such as AfuGprA; andmetalloproteases such as peptidase_M48.

In some instances, the fragmentation is a random fragmentation. In someinstances, the fragmentation generates specific lengths of proteinfragments, or the shearing occurs at particular sequence of amino acidregions.

In some instances, the protein fragments are further analyzed by aproteomic method such as by liquid chromatography (LC) (e.g. highperformance liquid chromatography), liquid chromatography-massspectrometry (LC-MS), matrix-assisted laser desorption/ionization(MALDI-TOF), gas chromatography-mass spectrometry (GC-MS), capillaryelectrophoresis-mass spectrometry (CE-MS), or nuclear magnetic resonanceimaging (NMR).

In some embodiments, the LC method is any suitable LC methods well knownin the art, for separation of a sample into its individual parts. Thisseparation occurs based on the interaction of the sample with the mobileand stationary phases. Since there are many stationary/mobile phasecombinations that are employed when separating a mixture, there areseveral different types of chromatography that are classified based onthe physical states of those phases. In some embodiments, the LC isfurther classified as normal-phase chromatography, reverse-phasechromatography, size-exclusion chromatography, ion-exchangechromatography, affinity chromatography, displacement chromatography,partition chromatography, flash chromatography, chiral chromatography,and aqueous normal-phase chromatography.

In some embodiments, the LC method is a high performance liquidchromatography (HPLC) method. In some embodiments, the HPLC method isfurther categorized as normal-phase chromatography, reverse-phasechromatography, size-exclusion chromatography, ion-exchangechromatography, affinity chromatography, displacement chromatography,partition chromatography, chiral chromatography, and aqueousnormal-phase chromatography.

In some embodiments, the HPLC method of the present disclosure isperformed by any standard techniques well known in the art. ExemplaryHPLC methods include hydrophilic interaction liquid chromatography(HILIC), electrostatic repulsion-hydrophilic interaction liquidchromatography (ERLIC) and reverse phase liquid chromatography (RPLC).

In some embodiments, the LC is coupled to a mass spectroscopy as a LC-MSmethod. In some embodiments, the LC-MS method includes ultra-performanceliquid chromatography-electrospray ionization quadrupole time-of-flightmass spectrometry (UPLC-ESI-QTOF-MS), ultra-performance liquidchromatography-electrospray ionization tandem mass spectrometry(UPLC-ESI-MS/MS), reverse phase liquid chromatography-mass spectrometry(RPLC-MS), hydrophilic interaction liquid chromatography-massspectrometry (HILIC-MS), hydrophilic interaction liquidchromatography-triple quadrupole tandem mass spectrometry (HILIC-QQQ),electrostatic repulsion-hydrophilic interaction liquidchromatography-mass spectrometry (ERLIC-MS), liquid chromatographytime-of-flight mass spectrometry (LC-QTOF-MS), liquidchromatography-tandem mass spectrometry (LC-MS/MS), multidimensionalliquid chromatography coupled with tandem mass spectrometry(LC/LC-MS/MS). In some instances, the LC-MS method is LC/LC-MS/MS. Insome embodiments, the LC-MS methods of the present disclosure areperformed by standard techniques well known in the art.

In some embodiments, the GC is coupled to a mass spectroscopy as a GC-MSmethod. In some embodiments, the GC-MS method includes two-dimensionalgas chromatography time-of-flight mass spectrometry (GC*GC-TOFMS), gaschromatography time-of-flight mass spectrometry (GC-QTOF-MS) and gaschromatography-tandem mass spectrometry (GC-MS/MS).

In some embodiments, CE is coupled to a mass spectroscopy as a CE-MSmethod. In some embodiments, the CE-MS method includes capillaryelectrophoresis-negative electrospray ionization-mass spectrometry(CE-ESI-MS), capillary electrophoresis-negative electrosprayionization-quadrupole time of flight-mass spectrometry (CE-ESI-QTOF-MS)and capillary electrophoresis-quadrupole time of flight-massspectrometry (CE-QTOF-MS).

In some embodiments, the nuclear magnetic resonance (NMR) method is anysuitable method well known in the art for the detection of one or morecysteine binding proteins or protein fragments disclosed herein. In someembodiments, the NMR method includes one dimensional (1D) NMR methods,two dimensional (2D) NMR methods, solid state NMR methods and NMRchromatography. Exemplary 1D NMR methods include ¹Hydrogen, ¹³Carbon,¹⁵Nitrogen, ¹⁷Oxygen, ¹⁹Fluorine, ³¹Phosphorus, ³⁹Potassium, ²Sodium,³³Sulfur, ⁸⁷Strontium, ²⁷Aluminium, ⁴³Calcium, ³⁵Chlorine, ³⁷Chlorine,⁶³Copper, ⁶⁵Copper, ⁵⁷Iron, ²⁵Magnesium, ¹⁹⁹Mercury or ⁶⁷Zinc NMRmethod, distortionless enhancement by polarization transfer (DEPT)method, attached proton test (APT) method and 1D-incredible naturalabundance double quantum transition experiment (INADEQUATE) method.Exemplary 2D NMR methods include correlation spectroscopy (COSY), totalcorrelation spectroscopy (TOCSY), 2D-INADEQUATE, 2D-adequate doublequantum transfer experiment (ADEQUATE), nuclear overhauser effectspectroscopy (NOSEY), rotating-frame NOE spectroscopy (ROESY),heteronuclear multiple-quantum correlation spectroscopy (HMQC),heteronuclear single quantum coherence spectroscopy (HSQC), short rangecoupling and long range coupling methods. Exemplary solid state NMRmethod include solid state ¹³Carbon NMR, high resolution magic anglespinning (HR-MAS) and cross polarization magic angle spinning (CP-MAS)NMR methods. Exemplary NMR techniques include diffusion orderedspectroscopy (DOSY), DOSY-TOCSY and DOSY-HSQC.

In some embodiments, the protein fragments are analyzed by method asdescribed in Weerapana et al., “Quantitative reactivity profilingpredicts functional cysteines in proteomes,” Nature, 468:790-795 (2010).

In some embodiments, the results from the mass spectroscopy method areanalyzed by an algorithm for protein identification. In someembodiments, the algorithm combines the results from the massspectroscopy method with a protein sequence database for proteinidentification. In some embodiments, the algorithm comprises ProLuCIDalgorithm, Probity, Scaffold, SEQUEST, or Mascot.

In some embodiments, a value is assigned to each of the protein from theprobe-protein complex. In some embodiments, the value assigned to eachof the protein from the probe-protein complex is obtained from the massspectroscopy analysis. In some instances, the value is thearea-under-the curve from a plot of signal intensity as a function ofmass-to-charge ratio. In some embodiments, a first value is assigned tothe protein obtained from the first cell solution and a second value isassigned to the same protein obtained from the second cell solution. Insome instances, a ratio is calculated between the two values. In someinstances, a ratio of greater than 2 indicates that the protein is acandidate for interacting with a drug. In some instances, the ratio isgreater than 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, or 20. In some cases, the ratio is at most 20.

In some instances, the ratio is calculated based on averaged values. Insome instances, the averaged value is an average of at least two, three,or four values of the protein from each cell solution, or that theprotein is observed at least two, three, or four times in each cellsolution and a value is assigned to each observed time. In someinstances, the ratio further has a standard deviation of less than 12,10, or 8.

In some instances, a value is not an averaged value. In some instances,the ratio is calculated based on value of a protein observed only oncein a cell population. In some instances, the ratio is assigned with avalue of 20.

Kits/Article of Manufacture

Disclosed herein, in certain embodiments, are kits and articles ofmanufacture for use with one or more methods described herein. In someembodiments, described herein is a kit for generating a proteincomprising a photoreactive ligand. In some embodiments, such kitincludes photoreactive small molecule ligands described herein, smallmolecule fragments or libraries and/or controls, and reagents suitablefor carrying out one or more of the methods described herein. In someinstances, the kit further comprises samples, such as a cell sample, andsuitable solutions such as buffers or media. In some embodiments, thekit further comprises recombinant proteins for use in one or more of themethods described herein. In some embodiments, additional components ofthe kit comprises a carrier, package, or container that iscompartmentalized to receive one or more containers such as vials,tubes, and the like, each of the container(s) comprising one of theseparate elements to be used in a method described herein. Suitablecontainers include, for example, bottles, vials, plates, syringes, andtest tubes. In one embodiment, the containers are formed from a varietyof materials such as glass or plastic.

The articles of manufacture provided herein contain packaging materials.Examples of pharmaceutical packaging materials include, but are notlimited to, bottles, tubes, bags, containers, and any packaging materialsuitable for a selected formulation and intended mode of use.

For example, the container(s) include probes, test compounds, and one ormore reagents for use in a method disclosed herein. Such kits optionallyinclude an identifying description or label or instructions relating toits use in the methods described herein.

A kit typically includes labels listing contents and/or instructions foruse, and package inserts with instructions for use. A set ofinstructions will also typically be included.

In one embodiment, a label is on or associated with the container. Inone embodiment, a label is on a container when letters, numbers or othercharacters forming the label are attached, molded or etched into thecontainer itself; a label is associated with a container when it ispresent within a receptacle or carrier that also holds the container,e.g., as a package insert. In one embodiment, a label is used toindicate that the contents are to be used for a specific therapeuticapplication. The label also indicates directions for use of thecontents, such as in the methods described herein.

Certain Terminology

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in theart to which the claimed subject matter belongs. It is to be understoodthat the foregoing general description and the following detaileddescription are exemplary and explanatory only and are not restrictiveof any subject matter claimed. In this application, the use of thesingular includes the plural unless specifically stated otherwise. Itmust be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise. In this application, theuse of “or” means “and/or” unless stated otherwise. Furthermore, use ofthe term “including” as well as other forms, such as “include”,“includes,” and “included,” is not limiting.

As used herein, ranges and amounts can be expressed as “about” aparticular value or range. About also includes the exact amount. Hence“about 5 μL” means “about 5 μL” and also “5 μL.” Generally, the term“about” includes an amount that would be expected to be withinexperimental error.

The section headings used herein are for organizational purposes onlyand are not to be construed as limiting the subject matter described.

The term “protein”, as used herein, refers to any polymeric chain ofamino acids. The term “protein” encompasses native or modified protein,protein fragments, or polypeptide analogs comprising non-native aminoacid residues. In some instances, a protein is monomeric. In otherinstances, a protein is polymeric. In some instances, a proteindescribed herein is also referred to as an “isolated polypeptide”, or apolypeptide that by virtue of its origin or source of derivation is notassociated with naturally associated components that accompany it in itsnative state; is substantially free of other proteins from the samespecies; is expressed by a cell from a different species; or does notoccur in nature.

In some embodiments, the term “bind(s)” or “binding” encompass acovalent interaction between a small molecule ligand and a proteinbinding site described herein. In other embodiments, the term “bind(s)”or “binding” encompass a non-covalent interaction between a smallmolecule ligand and a protein binding site described herein. Inadditional embodiments, the term “bind(s)” or “binding” encompass aninteraction between a small molecule ligand and a region of a protein ofinterest in which the region on the protein is about 1 Å, 2 Å, 3 Å, 4 Å,5 Å, 6 Å, 7 Å, 8 Å, 9 Å or 10 Å away from a binding site on the proteinof interest. In some cases, the binding site is a functional or activesite on the protein. In some cases, the binding site on the protein isnot a functional or active site. In additional cases, the binding siteon the protein is distal from a functional or active site. In thecontext of a competition interaction with two or more different smallmolecule ligands, the term “bind(s)” or “binding” can encompass blockingor displacement of small molecule ligands from interacting with a regionor binding site on a protein of interest.

As used herein, the term “functional site” or “active site” are usedinterchangeably and refer to a region of a protein that has a specificbiological activity. For example, the functional site can be a site thatbinds a substrate or other binding partner and optionally contributesthe amino acid residues that directly participate in the making andbreaking of chemical bonds. In some instances, a functional site oractive site encompass, e.g., catalytic sites of enzymes, ligand bindingdomains of receptors, binding domains of regulators, or receptor bindingdomains of secreted proteins. In some cases, the functional or activesite also encompass transactivation, protein-protein interaction, or DNAbinding domains of transcription factors and regulators.

EXAMPLES

These examples are provided for illustrative purposes only and not tolimit the scope of the claims provided herein.

Example 1—Cell Lines

HEK293T cells were maintained in high-glucose DMEM (Gibco) supplementedwith 10% (v/v) fetal bovine serum (FBS), penicillin (100 U/mL),streptomycin (100 μg/mL) and L-glutamine (2 mM). K562 and HSC-5 cellswere maintained in high-glucose IMDM (Gibco) supplemented with 10% (v/v)fetal bovine serum (FBS), penicillin (100 U/mL) and streptomycin (100μg/mL). All cell lines were grown at 37° C. in a humidified 5% CO2atmosphere. For SILAC experiments, each cell line was passaged at leastsix times in either SILAC DMEM or SILAC IMDM, (Thermo), which lackL-lysine and L-arginine, and supplemented with 10% (v/v) dialyzed FBS(Gemini), PSQ (as above), and either [¹³C6, ¹⁵N₂]-L-lysine and [¹³C6,¹⁵N₄]-L-arginine (100 μg/mL each) or L-lysine.HCl and L-arginine.HCl(100 μg/mL each). Heavy and light cells were maintained in parallel andcell aliquots were frozen after six passages in SILAC media and storedin liquid N₂ until needed. Whenever thawed, cells were passaged at leastthree times before being used in experiments.

3T3-L1 preadipocytes were maintained in DMEM supplemented with 10%bovine calf serum. 10T1/2 cells were maintained in DMEM with 10% fetalbovine serum (FBS). To induce differentiation, confluent cells werecultured in DMEM with 10% FBS and exposed to dexamethasone (1 μM),3-isobutyl-1-methylxanthine (IBMX; 0.5 mM), and insulin (1 μg/ml) for 2days, followed by culture with insulin alone (1 μg/ml).

Example 2—In Situ Labeling of Live Cells with “Fully Functionalized”Fragment (FFF) Probes

For gel-based experiments, cells were grown in 6-well plates to ˜90%confluence at the time of treatment. Cells were carefully washed withDulbecco's phosphate buffered saline (DPBS) and replenished with freshserum-free media containing indicated FFF probe, and, if applicable,competitors or DMSO vehicle (1 mL). Following incubation at 37° C. for30 min, cells were directly exposed to 365 nm light for 10 min. For noUV experiments, cells were incubated at 4° C. for 10 min under ambientlight. For MS-based experiments, cell labeling was performed in asimilar manner as described above. Modifications to this protocolincluded using isotopically ‘light’ and ‘heavy’ SILAC cells that weregrown to near complete confluence prior to treatment in 10 cm plates. Inprobe-versus-control probe and probe-versus-probe experiments,isotopically light cells were treated with indicated fragment probe,while the heavy cells were treated with control probe (1), or additionalFFF probe to be compared, at indicated concentrations. In competitiontype experiments, heavy and light cells were co-treated with theindicated FFF probe and competitor or DMSO, respectively. Followingtreatments and photocrosslinking, cells were harvested in cold DPBS byscraping, centrifuged (1,400 g, 3 min, 4° C.), and pellets washed withcold DPBS (2×) and then aspirated. Pellets were either directlyprocessed or kept frozen at −80° C. until use.

Example 3—Preparation of Probe-Labeled Proteome for Gel- and MS-BasedProtein Analyses

Cells pellets were lysed in cold DPBS (100-500 □L) using a BransonSonifier probe sonicator (10 pulses, 30% duty cycle, output setting=4).For experiments requiring cell fractionation into membrane and solubleproteomes, cell lysates were then centrifuged (100,000×g, 45 min) toprovide soluble (supernatant) and membrane (pellet) fractions. Membranepellets were resuspended in cold DPBS after separation by sonication.Protein concentration was determined using the DC Protein Assay(Bio-Rad) and absorbance read using a Tecan, Infinite F500 plate readerfollowing manufacturer's instructions. For SILAC experiments,isotopically heavy and light whole cell lysates were adjusted to 1.5mg/mL, and were then mixed in equal proportions (500 □L each) in coldDPBS.

Example 4—Gel-Based Analysis of Crosslinked Proteins in Cells

Proteomes from treated cells were diluted to 1 mg/mL. To each sample (50□L), 6 □L of a freshly prepared “click” reagent mixture containing 0.1mM tris(benzyltriazolylmethyl)amine (TBTA) (3 □L/sample, 1.7 mM in 1:4DMSO:t-ButOH), 1 mM CuSO₄ (1 □L/sample, 50 mM in H₂O), 25 □Mtetramethylrhodamine (TAMRA) azide (1 □L/sample, 1.25 mM in DMSO), andfreshly prepared 1 mM tris(2-carboxyethyl)phosphine HCl (TCEP) (1□L/sample, 50 mM in PBS or H₂O) was added to conjugate the fluorophoreto probe-labeled proteins. Upon addition of the click mixture, eachreaction was immediately mixed by vortexing and then allowed to react atambient temperature for 1 hr before quenching the reactions with SDSloading buffer (4× stock, 17 □L). Proteins (25 □g total protein loadedper gel lane) were resolved using SDS-PAGE (10% acrylamide) andvisualized by in-gel fluorescence on a Hitachi FMBIO-II or a Bio-RadChemiDoc™ MP flatbed fluorescence scanner.

Example 5—Preparation of Labeled Proteome for MS-Based Analysis

Profiling experiments were adapted methods previously reported. To thecombined mixture of heavy and light soluble proteomes (1.5 mg) in 1 mLDPBS, a mixture of TBTA (60 μL/sample, 1.7 mM in 1:4 DMSO:t-BuOH), CuSO₄(20 μL/sample, 50 mM in H₂O), TCEP (20 μL/sample, 50 mM in DPBS) andBiotin-N3 (10 μL/sample, 10 mM in DMSO) was added and each sample wasrotated at room temperature. After 1 hr, the mixture was transferred toa 15 mL falcon tube and a cold 4:1 mixture (2.5 mL) of methanol(MeOH)/chloroform (CHCl₃) was added followed by cold PBS (1 mL) on ice.The resulting cloudy mixture was centrifuged (5,000×g, 10 min, 4° C.) tofractionate the protein interphase from the organic and aqueous solventlayers. After washing the protein disc carefully with cold 1:1MeOH:CHCl₃ (3×1 mL) followed by sonication in cold 4:1 MeOH:CHCl₃ (3 mL)to ensure click reagents were efficiently removed, the remainingprecipitate was pelleted by centrifugation (5,000×g, 10 min, 4° C.). Thepellet was aspirated and resuspended in a freshly-prepared solution ofproteomics-grade urea (500 μL, 6 M in DPBS) containing 10 μL of 10% SDSand then dissolved by sonication. Disulfides were reduced by adding 50μL of a 1:1 mixture containing TCEP (200 mM in DPBS) pre-neutralizedwith potassium carbonate (600 mM DPBS) for 30 min at 37° C. Reducedthiols were then alkylated by addition of iodoacetamide (70 μL of 400 mMin DPBS) for 30 min at ambient temperature protected from light. To eachsolution, 130 μL of 10% SDS (in DPBS) was added and then diluted to˜0.2% SDS with DPBS (5.5 mL) and incubated with pre-equilibratedstreptavidin agarose resin (100 μL 1:1 slurry, Pierce) for 1.5 hr atambient temperature on a rotator. The streptavidin beads were collectedby centrifugation (1,400 g, 1-2 min) and sequentially washed with 0.2%SDS in DPBS (1×5 mL), detergent-free DPBS (2×5 mL), and H₂O (2×5 mL) toremove unbound protein, excess detergent, and small molecules. The resinwas transferred to a Protein LoBind tube (Eppendorf) and bound proteinswere digested on-bead overnight at 37° C. in ˜200 μL total volumecontaining sequencing grade porcine trypsin (2 μg, Promega) in thepresence of urea (2 M in DPBS) and CaCl₂ (1 mM). The proteolyzedsupernatant was transferred to a fresh Protein LoBind tube, acidifiedwith formic acid (5% final) and stored at −20° C. until analyzed.

Example 6—Multidimensional Liquid Chromatography-Tandem MassSpectrometry (LC/LC-MS/MS) Analysis of Tryptic Digests

Peptides from tryptic digests were pressure loaded onto a 250 μm (innerdiameter) fused silica capillary column packed with C18 resin (4 cm,Aqua 5 μm, Phenomenex). Samples were analyzed using an LTQ-OrbitrapVelos mass spectrometer (Thermo Scientific) coupled to an Agilent 1200series quaternary pump. Peptides were eluted by two-dimensionalseparation on a column with a 5 μm tip [100 μm fused silica, packed withC18 (10 cm) and strong cation exchange (SCX) resin (4 cm, Phenomenex)]using a five-step ‘MudPIT’ protocol that involves 0%, 25%, 50%, 80% and100% salt bumps of ammonium acetate (NH₄OAc; 500 mM) to elute peptidesstepwise from the SCX to the C18 resin followed by an increasinggradient of acetonitrile in each step (5%-100% buffer B in buffer A;buffer A: 95% H₂O, 5% acetonitrile, 0.1% formic acid; buffer B: 5% H₂O,95% acetonitrile, 0.1% formic acid). The flow rate through the columnwas 0.25 μl/min and the voltage applied to the nano-LC electrosprayionization source was 2.5 kV. Spectra were collected in a data-dependentacquisition mode such that each scan cycle involved a singlehigh-resolution full MS spectrum of parent ions (MS1 scan from 400-1800m/z) collected in the orbitrap coupled to 30 CID-induced fragmentation(MS2) scans in the ion trap of the 30 most abundant parent ions from theMS1 scan. Dynamic exclusion (repeat count of 1, exclusion duration of 20s). Parent ions with unassigned or +1 charge states by the instrumentwere excluded for fragmentation. All other parameters were left atdefault values.

Example 7—Peptide and Protein Identification and Quantification

From each of the five .raw files (one for each salt ‘bump’) generated bythe instrument (Xcalibur software), the MS2 spectra for all fragmentedparent ions (.ms2 file) were extracted using RAW Xtract (version1.9.9.2; 2004 release). Each .ms2 file was searched using the ProLuCIDalgorithm against a reverse-concatenated, nonredundant (gene-centric)database of the human proteome (Uniprot release—Nov. 5, 2012) or mouseproteome (Nov. 5, 2012) and filtered using DTASelect 2.0 within theIntegrated Proteomics Pipeline (IP2) software. All cysteine residueswere specified with a static modification for carbamidomethylation(+57.0215 Da) and one oxidized methionine residue per peptide (if found)was allowed as a variable oxidation (+15.9949 Da). In addition, peptideswere required to have at least one tryptic terminus. Each dataset wassimultaneously searched for both light and heavy isotopologues of thesame peptide by specifying the mass shift of heavy residues as staticmodifications on lysine (+8.0142 Da) and arginine (+10.0082 Da) in acoupled ‘heavy’ search. The precursor ion mass tolerance for a minimumenvelope of three isotopic peaks was set to 50 ppm, the minimum peptidelength was six residues, the false-positive rate was set at 1% or lowerand at least 2 peptides of a protein must be detected in order to beadvanced to the next step of analysis.

Heavy and light parent ion chromatograms associated with successfullyidentified peptides were extracted and compared using in-house software(CIMAGE). Briefly, extracted MS1 ion chromatograms (+10 ppm errortolerance of predicted m/z) from both ‘light’ and ‘heavy’ target peptidemasses (m/z) were generated using a retention time window (+10 min)centered on the time when the peptide ion was selected for MS/MSfragmentation (minimum 3 MS1's per peak), and subsequently identified.Next, the ratio of the peak areas under the light and heavy signals(signal-to-noise ratio>2.5) was calculated. Computational filters usedto ensure that the correct peak-pair was used for quantification includea co-elution correlation score filter (R2≥0.8), removing target peptideswith bad co-elution profile, and an ‘envelope correlation score’ filter(R2>0.8) that eliminates target peptides whose predicted pattern of theisotopic envelope distribution does not match the experimentallyobserved high-resolution MS1 spectrum. In addition, peptides detected as‘singletons,’ where only the heavy ion of a peptide pair was identified,but that cleared all other filtering parameters, are given a defaultassigned ratio of ‘20,’ which is defined as any measured ratio that is≥20 and is the maximum ratio reported here.

Example 8—Proteomic Analysis of Probe-Labeled Proteins by MassSpectrometry

Median SILAC ratios were filtered to ensure that each protein ratio wasresultant from three or more unique and quantified peptides and that thecombined peptide ratios possessed a standard deviation of less than 60%of the median; if greater, the combined ratio was assigned the lowestquantified peptide value. SILAC ratios meeting these criteria were thencombined with replicate data sets from the same probe, cell line andexperimental conditions. Identification of probe targets enriched infragment probe versus control probe experiments in HEK293T cellsrepresent averaged data from at least two biological replicateexperiments and K562 data in single replicate experiments.Identification of probe targets from comparison of probe versus probeexperiments and from fragment probe competition experiments representaveraged values of at least two biological replicate experiments.

In order to be classified as a probe target, proteins must (1) complywith the above criteria and (2) be enriched greater than 5-fold overcontrol probe 1 (SILAC>5) in at least two different probe data sets (200μM). If protein is enriched 5-fold or more by only one probe, then ithad to be quantified in three or more independent experiments. In orderto be included in probe-versus-probe comparisons, protein must abide bythe above criteria and also be a target for at least one of the twoprobes, as designated above. For competition experiments, proteins (1)must be designated probe targets for the probe being used, as describedabove, (2) competed greater than 3-fold (competition SILAC ratio>3)unless otherwise noted, and (3) must have SILAC ratios derived fromthree or more quantified peptides.

Example 9—Fragment Probe Target Meta-Analysis

Custom python scripts were used to compile functional annotations offinal probe targets available in the UniProtKB/Swiss-Prot ProteinKnowledge database. Probe targets were queried against the DrugBankdatabase (Version 4.2) and fractionated into DrugBank and non-DrugBankproteins. Functional keywords assigned at the protein level werecollected from the Uniprot database and the two DrugBank andnon-DrugBank categories were further classified into protein functionalclasses. Membrane proteins were defined as proteins possessing known orpredicted transmembrane domains (UniProt analysis), and the remainingtargets were considered soluble. Heatmaps were generated using RStudiosoftware.

Example 10—Cell Treatments and Preparation for MS-Based Analyses ofProbe-Modified Peptides

Preparation and analysis was adapted from methods previously reported.In brief, for global mapping of fragment probe-modified peptides,separate 10 cm dishes of cells were treated with probes (200-250 μM) in3.0 mL of DMEM (serum-free) and (if applicable) competitor ligands,proteomes harvested and subjected to click chemistry conditions witheither light or heavy isotopically labeled biotin-TEV-azide (10 μL of 5mM stocks in DMSO, final concentration=100 μM), TCEP, ligand and CuSO₄as detailed above. The samples were allowed to react for 1 h at whichpoint the samples were centrifuged (16,000 g, 5 min, 4° C.). Theresulting pellets were sonicated in ice-cold methanol (500 μL) and theresuspended light- and heavy-labeled samples were then combined andcentrifuged (16,000 g, 5 min, 4° C.). The pellets were then solubilizedin PBS containing 1.2% SDS (1 mL) with sonication and heating (5 min,95° C.). Samples were transferred to falcon tubes containing DPBS (5mL), to which a 100 μL of streptavidin-agarose beads slurry was added.After incubation, the beads (3 hr) were pelleted by centrifugation(1,400 g, 3 min) and were washed (2×10 mL PBS and 2×10 mL water). Thebeads were transferred to eppendorf tubes with 1 mL DPBS, centrifuged(1,400 g, 3 min), and resuspended in PBS containing 6 M urea. To thiswas added 10 mM DTT (25 μL of a 200 mM stock in water) and the beadswere incubated at 65° C. for 15 mins. 20 mM iodoacetamide (25 μL of a400 mM stock in water) was then added and allowed to react at 37° C. for30 mins with shaking. The bead mixture was diluted with 900 μL PBS,pelleted by centrifugation (1,400 g, 3 min), and resuspended in 200 μL2M urea (DPBS) containing trypsin and CaCl₂ as described above. Thebeads were separated from the digest by centrifugation (1,000 g, 1 min),washed (2×1 mL PBS and 2×1 mL water) and then transferred to fresheppendorfs with 1 mL water. The washed beads were washed once further in150 μL TEV buffer (50 mM Tris, pH 8, 0.5 mM EDTA, 1 mM DTT) bycentrifugation (1,400 g, 3 min) and the resuspended in 150 μL TEVbuffer. 5 μL TEV protease (80 μM) was added and the reactions wererotated overnight at 29° C. The TEV digest was separated from the beadsby centrifugation (1,400 g, 3 min) and the beads were washed once withwater (100 μL). The samples were then acidified to a final concentrationof 5% (v/v) formic acid and stored at −80° C. prior to analysis.

The resulting probe-modified peptides were collected for MS analysis,which was performed as described above with differences in the saltbumps applied in the chromatographic gradients which in this case were0%, 30%, 60%, 90% and 100% NH₄OAc (500 μM). The protein identificationsearches of the MS data were performed with the following changesapplied to identify the peptides modified with the correspondingfragment probe and the cleaved TEV tag. All amino acids were consideredas possible residues for modification. To facilitate the computationalsearches, sets of up to 3 amino acids were searched using ProLuCID andfiltered with DTASelect as described above. The mass of the modificationused to search for probe-modified peptides was +665.4013 m/z for 8,+667.3264 m/z for 4, +665.3285 m/z for 3, +678.3602 m/z for 6, +680.4122m/z for 9, +679.4179 m/z for 13, +755.3867 m/z for 2, +655.4170 m/z for14, and +669.3598 m/z for 15, which are the masses for the correspondingprobe plus the light TEV-tag and an additional +6.0138 m/z for the heavycounterpart. The isoTOP ratios for probe labeled peptides werequantified using the in-house software CIMAGE.

Example 11—Analysis of Probe Labeled Peptides

For protein mapping experiments, fragment probe-modified peptides wereexpected to show a ratio of heavy and light signals of ˜1.0(0.5<ratio<2.0) and were required to have been designated an enrichedtarget by the corresponding probe in whole-protein capture experiments.For each protein in the site-of-labeling dataset, the UniProtKBaccession number was used to map and collect relevant structures fromthe RCSB Protein Data Bank (PDB) fulfilling the following criteria:structures determined by X-ray crystallography, wild-type protein, Homosapiens as the sole source organism. For proteins with multipleavailable structures, custom R scripts were used to further filter thePDB files, privileging higher sequence coverage for isoTOP peptides (seeTables 1-3 for selected PDB accessions). Fpocket 2.0 was used to detectpotential binding pockets for the resultant structures with allparameters set at recommended default. Pockets with volume less than 500Å³ were removed from output prior to further analysis. Residuessurrounding fpocket predicted binding pockets for each protein werecollected to determine the number of residues overlapping with isoTOPpeptides. For structures with multiple chains, the average number ofoverlapping residues for all chains possessing isoTOP peptide was used.Custom Python scripts were used to compile functional site annotationsusing the UniProtKB/Swiss-Prot Protein Knowledge database(release-2016_06). Relevant UniProt entries were searched for availablefunctional residues, specifically for annotations regarding enzymecatalytic residues (active sites), substrate binding sites, andmetal-binding sites. At the isoTOP peptide level, the distances betweenall possible atom pairs, consisting of one atom from isoTOP peptide andthe other atom from a functional site, were calculated and the minimumdistance was designated as the spatial distance between isoTOP peptideand functional sites. Annotated FFF-labeled peptides and correspondinganalyses shown in Table 1-3.

Example 12—PPARγ Luciferase Reporter Assay

HEK293T cells were transiently co-transfected using Polyethylenimine(Sigma) with a UAS-Luciferase reporter and a vector expressing theheterologous GAL4 DNA binding domain (DBD) or a GAL4 DNA bindingdomain::PPARγ ligand binding domain (LBD) chimeric protein, andfull-length PTGR2. 24 hr after transfection, cells were treated eitherwith vehicle (DMSO), 15k-PGE₂ (20 μM), or fragment compounds.Rosiglitazone (2 μM), a synthetic PPARγ ligand, was used as control. 16hr after incubation, cells were lysed in Cell Culture Lysis Reagent(Promega) and luciferase activity measured using the Luciferase AssaySystem (Promega).

Example 13—Oxygen Consumption Rate Measurements

Palmitate-BSA oxidation measurements were performed using the SeahorseXFe96 Extracellular Flux Analyzer. Briefly, HSC5 cells were plated at4.0×10⁴ cells/well and incubated for 24 hr in a 37° C., 5% CO₂incubator. One hour prior to the XF assay, media was changed to 1×Krebs-Henseleit buffer (111 mM NaCl, 4.7 mM KCl, 2 mM MgSO₄, 1.2 mMNa₂HPO₄, pH 7.4) with 2.5 mM glucose, 0.5 mM carnitine, and 5 mM HEPES.20 min after media exchange, cells were treated with either vehicle(DMSO), 24 (100 μM) or 21 (100, 50, 20 and 5 μM respectively). After 40min, cells were given palmitate:BSA (667 μM and 167 μM respectively) orBSA alone and the XF assay was started. Perturbation compounds(oligomycin 4 μM, FCCP 4 μM, RAA 2 μM) were prepared in 1× KH buffer andinjected from the reagent ports automatically onto wells.

Example 14—Adipocyte Phenotypic Screen

3T3-L1 preadipocytes were induced to differentiate in the presence of 50μM of each fragment probe. Rosiglitazone (2 μM) was used as a positivecontrol. Media was replaced every two days and compounds refreshed. Onday 8 of differentiation, cells were fixed with 4% PFA and stained withthe fluorescent lipid stain Nile red (AdipoRed) and Hoechst for nucleicounterstain. Cells were imaged using a Celigo S Cell Imaging Cytometer(Nexcelom Bioscience) and compounds promoting increased lipidaccumulation (i.e. fluorescence) identified. Hits were validated at twoconcentrations (10 μM and 50 μM) in 12-well plate format. To prepareprimary brown preadipocytes, interscapular fat depots of neonatal micewere digested for 40 min at 37° C. with 1.5 mg/mL collagenase type I in61.5 mM NaCl, 2.5 mM KCl, 0.65 mM CaCl₂, 2.5 mM glucose, 50 mM Hepes, 50μg/mL penicillin-streptomycin and 2% (wt/vol) BSA. Cells were nextfiltered through a 100 μm cell strainer, plated in DMEM supplementedwith 20 mM Hepes, 20% FBS, and penicillin/streptomycin, and grown toconfluency. Cells were induced to differentiate in DMEM with 10% FBS,dexamethasone (1 μM), IBMX (0.5 mM), insulin (1 μg/ml), triiodothyronine(1 nM), and either DMSO (0.1%), 25 (10 μM), or rosiglitazone (2 μM). Twodays later, media was switched and differentiating cells were maintainedin DMEM, 10% FBS, insulin, triiodothyronine, and experimental compounds.Media was refreshed every 2 days. Human mesenchymal stem cells weremaintained in DMEM supplemented with 10% FBS and grown to confluence.Two days after confluence, cells were induced to differentiate in mediacontaining DMEM supplemented with 10% FBS, dexamethasone (1 μM), IBMX(0.5 mM), insulin (1 μg/ml), indomethacin (125 μM), and either DMSO(0.1%), 25 (10 μM), or rosiglitazone (2 μM) for 2 days. Media andcompounds were refreshed every 2 days, alternating completedifferentiation media with maintenance media (DMEM 10% FBS supplementedonly with insulin) for 18 days.

Example 15—RNAseq Analysis

For RNA-seq, 0.6-1×10⁶ cells were collected in Trizol (Invitrogen) andtotal RNA was extracted using Direct-Zol RNA extraction kit (ZymoResearch). PolyA+ RNA was fragmented and prepared into strand-specificlibraries using the Illumina True-seq stranded RNA kit (Illumina) andanalyzed on an Illumina HiSeq 2500 sequencer. Libraries were sequencedusing single-end 50 bp reads at a depth of 10-15 million reads perlibrary. Single-end sequencing reads were mapped to the mouse referencegenome (mm9, NCBI37) using STAR (version 2.3.0.c, default parameters).Only reads that aligned uniquely to a single genomic location were usedfor downstream analysis (MAPQ>10). Gene expression values werecalculated for read counts on exons of annotated RefSeq genes usingHOMER. Differentially expressed genes between GFP- andPGRMC2-overexpressing cells were calculated from three replicates percondition using EdgeR and a threshold of adjusted p-value<0.05 was usedto call differentially expressed genes. Gene expression values are shownas read counts normalized to 107 mapped reads. Differentially expressedgenes were used for pathway analysis. Gene ontology functionalenrichment analysis was performed using Ingenuity Pathway Analysis(Qiagen). Heatmaps were generated using RStudio software (package‘gplots’). RNA-seq data have been deposited in the GEO repository underaccession number GSE90731.

Example 16—Cell Viability Assay

Cells were seeded in white-opaque 96-well plates in full growth media ata density of 6,000 cells/well (100 μL) and were allowed to grow for 14hrs at 37° C. in a humidified 5% CO₂ atmosphere. The cells were thentreated with compounds or DMSO (1% DMSO final for all wells) intriplicate and incubated at 37° C. in a humidified 5% CO₂ atmosphere for45 min. Note, all photoaffinity probe incubations for MS- and gel-basedexperiments were performed for 30 min. Cell viability was determinedusing the luciferase-based CellTiter-Glo Luminescent Cell ViabilityAssay (Promega).

Example 17—Cloning and Transient Overexpression of Proteins in HEK293TCells

Full-length genes encoding proteins of interest were PCR amplified froma cDNA library derived from low-passage HEK293T cells. Gene productswere cloned into the pRK5 vector with a C-terminal FLAG tag using SalI(N-terminal) and NotI (C-terminal) restriction sites. All clonesequences were verified. To recombinantly overexpress proteins used inin situ treatments, HEK293T cells were grown to 40-60% confluency understandard growth conditions in 6-well (for gel-based experiments) or 10cm tissue culture plates (for MS-based experiments) and transientlytransfected with 1-3 μg of desired construct (6-well plates) or 5 μg (10cm plates) using polyethyleneimine ‘MAX’ (MW 40,000, PEI; Polysciences,Inc.). ‘Mock’ transfected cells were transfected with a vectorcontaining METAP2 for 48 hr. Human SLC25A20 in a pCMV6-Entry vector witha C-terminal DDK tag was purchased from Origene. Empty pCMV-Entry vectorwas used as ‘mock’ control for experiments with SLC25A20. The pRK5vector was a gift from David Sabatini (MIT).

Example 18—Lentiviral Infection

3T3-L1 preadipocytes were infected overnight at 70% confluency in 10 cmPetri dishes with lentiviruses expressing a non-targeting scramble shRNAor two different shRNAs against mouse PGRMC2. Two days after infection,cells were re-plated into 12-well plates and grown to confluence. Twodays after confluence, cells were induced to differentiate in presenceof dexamethasone (1 μM), IBMX (0.5 mM), insulin (1 μg/ml) and eitherDMSO (0.1%), test compound (10 μM), or Rosiglitazone (2 μM). Cells werestained at day 7 of differentiation with Nile Red and Hoechst, imagedand harvested for RNA and protein extraction. For rescue experiments,scramble and PGRMC2 knockdown cells were co-infected with lentivirusesover-expressing human V5-tagged PGRMC2. 3T3-L1 preadipocytes stablyoverexpressing GFP or hPGRMC2 were selected with blasticidin (20 μg/ml)for 10 days and maintained in culture in 10% BCS.

Example 19—Confocal Imaging of PGRMC2

For immunostaining, cells were grown on gelatin-coated cover glasses,fixed in 4% PFA, permeabilized in 0.5% Triton-PBS and blocked with 5%FBS-PBS solution. Rabbit anti-PGRMC2 (Bethyl Labs) and mouse KDELmonoclonal antibody (SEQ ID NO: 925) (clone 10C3, Enzo Life Sciences)were diluted at 0.4 μg/ml and 1 μg/ml using blocking buffer and sampleswere incubated overnight at 4° C. in a humidified chamber.Alexafluor-488 anti-rabbit and alexafluor-568 anti-mouse secondaryantibodies were diluted to 1:500 dilution in blocking buffer and samplesincubated for 1 hour at RT. Nuclei and actin filaments were stained byHoechst and Acti-stain 670 phalloidin dyes, respectively. Cells werewashed 3 times with PBS for 10 minutes after each incubation. Imageswere acquired with a Zeiss LSM 710 laser scanning confocal microscopeand analyzed with IMARIS (Bitplane Inc.) and Adobe Photoshop CS3 (AdobeSystems Incorporated) software.

Example 20—Western Blot Analysis

After scanning for fluorescence, proteins were transferred to anitrocellulose membrane in Towbin buffer, the membrane was blocked for˜1 hr at ambient temperature with 5% nonfat dry milk (w/v) or 5% BSA inTris-buffered saline with Tween 20 (TBST) and incubated with primaryantibodies in the same solution overnight at 4° C. The blots were washed(3×5 min, TBST), incubated with secondary antibodies (IRDye 800CW orHRP-conjugated anti-mouse and anti-rabbit) in milk or BSA for 1 hr atambient temperature, washed (3×5 min, TBST), rinsed in water andvisualized on a LICOR Odyssey Scanner or resolved by film exposure.

Example 21—Gene Expression Analysis

Total RNA was isolated from cells using Direct-zol™ RNA MiniPrep Plus(Zymo Research). Taqman-based quantitative real-time PCR was performedusing the SuperScript III Platinum One-Step qRT-PCR reagent (ThermoFisher Scientific). Samples were run in triplicate as multiplexedreactions and normalized to an internal control (36B4; acidic ribosomalphosphoprotein P0 mRNA).

Example 22—In Vitro LCMS-Based Activity Assay for PTGR2

Aliquots (1 μL) of test compounds dissolved in DMSO were transferred to1.5 mL eppendorf tubes followed by addition of recombinant human PTGR2(44 μL, 200 nM final concentration) in freshly prepared reaction buffer(Tris Buffer, 1 mM EDTA, 50 μM TCEP, 300 μM NADPH). The resultingmixture was vortexed and then incubated at 37° C. for 20 min. Next, a 5μL solution of 15-keto-PGE₂ substrate (20 μM final concentration) inreaction buffer was added and the reaction was allowed to proceed for 30min at 37° C. Reactions were quenched by the addition of 0.5% AcOH inethyl acetate (800 μL), water (300 μL) and 100 μL of internal standardPGE₂-d₄ (30 pmol/sample) dissolved in 1:1 methanol/water. Phases wereseparated by centrifugation and the organic layer was collected anddried under a stream of N₂, then stored at −80° C. until analysis.Directly prior to analysis, samples were reconstituted in 100 μL ofMeCN:H₂O (1:1, v/v) and analyzed by LC/MS/MS. All conditions wereperformed in triplicate and repeated at least three independent times.

LCMS Conditions for prostaglandin measurements Instrument Agilent 6460Triple Quadrupole LC/MS system Column Kinetex 5 μm C18 100 A, 50 × 4.6mm column Injection 15 μL Gas temperature 350° C. Gas flow 9 L/minnebulizer 35 psi capillary 4000 V positive/4000 V negative MRM scan type300 delta EMV (+) Mobile Phase A 70:30:0.1 H₂O/Acetonitrile/Formic acidMobile Phase B 50:50:0.1 Isopropyl Alcohol/Acetonitrile/Formic Acid

The following MS parameters were used to measure the indicatedmetabolites by MRM (precursor ion, product ion, collision energy,polarity): PGE₂-d₄ (355, 275, 18), 13,14-dihydro-15-keto-PGE₂ (351, 333,18) and 15-keto-PGE₂ (349, 161, 20). 15-keto-PGE₂ and13,14-dihydro-15-keto-PGE₂ levels were quantified by determining peakareas in relation to internal standard PGE₂-d₄. Non-deuterated15-keto-PGE₂ and 13,14-dihydro-15-keto-PGE₂ standards were used toconfirm retention time and fragmentation.

Chromatography Method

Time (min) B (%) Flow rate (mL/min) 0.0 0 0.6 1.0 0 0.6 2.0 20 0.6 4.020 0.6 7.0 75 0.6 7.2 100 0.6 11.0 100 0.6 11.1 0 0.6 13.0 0 0.6

-   -   To minimize carryover, LC solvents were cycled between 100%        Mobile Phase A and 100% Mobile Phase B over 5 min after each        run.

Example 23—LCMS Analysis of Acylcarnitines in HSC-5 Cells

HSC-5 cells were seeded in 10 cm plates and grown to ˜90% confluency.Media was aspirated, cells were washed carefully with DPBS (3 mL) andresuspended in freshly-prepared serum-free IMDM media containing testcompound(s) or vehicle. After incubation at 37° C. for 3 hr, the mediawas removed and cells were washed with cold DPBS (2×3 mL). Cells werescraped in 4 mL cold DPBS, transferred to a falcon tube and centrifugedat 2000 rpm for 8 min, and resuspended in 1 mL cold DPBS. Cells werelysed using a probe sonicator, and 1 mL of lysates normalized to 1.5mg/mL were transferred to 2-dram glass vials. MeCN (3 mL) containingacyl carnitine internal standard mix (Cambridge Isotope Laboratories)was added to lysates and vigorously vortexed. Internal standards include²H₉-carnitine (2.28 nmol); ²H₃-acetyl carnitine (C2, 570 pmol); ²H₃propionyl carnitine (C3, 120 pmol); ²H₃ butryl carnitine (C4, 120 pmol);²H₉ isovaleryl carnitine (C5, 120 pmol); ²H₃ octanoyl carnitine (C8, 120pmol); ²H₉ myristoyl carnitine (C14, 120 pmol); ²H₃ palmitoyl carnitine(C16, 240 pmol). Samples were centrifuged at 1000 rpm for 5 min topellet insoluble precipitate, and the remaining eluent carefullytransferred to fresh 2-dram vials to avoid disturbing the precipitate.The eluent was concentrated under a stream of N₂, and samples werestored at −80° C. until analysis. Directly prior to analysis, sampleswere reconstituted in 500 uL of MeCN:H₂O (1:1, v/v) and analyzed byLC/MS/MS. The indicated acyl carnitines were quantified by measuring thearea under the peak relative to an internal standard (2H₃ palmitoylcarnitine for C16, C18 and C18:1; ²H₉ myristoyl carnitine for C12 andC14; ²H₃ octanoyl carnitine for C5DC/C10-OH and C4DC; ²H₉ isovalerylcarnitine for C5 and C7).

LCMS Conditions for acyl carnitine measurements Instrument Agilent 6460Triple Quadrupole LC/MS system Column Kinetex 5 μm C18 100 A, 50 × 4.6mm column Injection 15 μL Gas temperature 350° C. Gas flow 9 L/minnebulizer 35 psi capillary 4000 V positive/4000 V negative MRM scan type300 delta EMV (+) Mobile Phase A 95:5:0.1 H₂O/Methanol/Formic AcidMobile Phase B 60:35:5:0.1 Isopropyl Alcohol/Methanol/H₂O/Formic AcidChromatography Method:

Time (min) % B Flow (mL/min) 0 0 0.1 5 0 0.1 5.01 0 0.4 7 0 0.4 30 1000.4 30.01 100 0.5 38 100 0.5 38.01 0 0.5 42 0 0.5 46 100 0.5 50 100 0.554 0 0.5 57 0 0.5 57.01 0 0.4 59 0 0.1

-   -   To minimize carryover, LC solvents were cycled between 100%        Mobile Phase A and 100% Mobile Phase B over 5 min after each        run.        Transition Table:

Transition Table: Acyl Carnitine Precursor → product ion C12 344.2 →85.1 C14 372.3 → 85.1 C16 400.3 → 85.1 C18:1 426.3 → 85.1 C18 428.3 →85.1 C4DC 318.2 → 85.1 C5 246.1 → 85.1 C10-OH 332.2 → 85.1 C7 274.1 →85.1 D3 acetyl 207.1 → 85.1 D3 butyryl 235.1 → 85.1 D3 octanoyl 291.2 →85.1 D3 palmitoyl 403.3 → 85.1 D3 propionyl 221.1 → 85.1 D9 isovaleryl255.1 → 85.1 D9 myristoyl 381.3 → 85.1

Example 24—Quantification and Statistical Analysis

All data fitting and statistical analysis performed using GraphPad Prismversion 6.00 for Windows, GraphPad Software, La Jolla Calif. USA,www.graphpad.com. Statistical values including the exact n andstatistical significance are also reported. Probe binding blockade andPTGR2 inhibition curves are plotted as mean±SD (n=3 or 4 per group) fora representative biological replicate using a variable slope (fourparameter) non-linear fit. Gene expression data are presented as mean±SD(n=3 per group). HSC5 metabolite data are shown as mean±SD (n=3 pergroup). Statistical significance was defined as P<0.05 and determined by2-tailed Student t tests, or two-way ANOVA with Bonferroni's post-tests.

Example 25—Data and Software Availability

Data Resources: The RNA-seq data reported has been deposited in the NCBIunder the ID code GEO: GSE90731.

Software: All custom scripts used have been deposited to GitHub(https://github.com/Chymichead/FBDDinCell).

Example 26—Profiling Small-Molecule Fragment-Protein Interactions inHuman Cells

A small library of 14 “fully functionalized” fragment (FFF) probes weresynthesized as described in Example 30 with each member possessing avariable small-molecule fragment conjugated to a constant tag bearing analkyne and photoactivatable diazirine group (FIG. 1A). The variablefragment groups had an average molecular weight of 176 Da and wereselected because they represent structural motifs found in manybiologically active natural products and clinically approved drugs (FIG.1B). The FFF probes were initially assessed using gel-based profiling(FIG. 1D) by treating HEK293T cells with each fragment probe (20 μM, 30min), followed by exposure to UV light (10 min, 4° C.), cell lysis,coupling to a rhodamine (Rh)-azide tag using copper-catalyzed azidealkyne cycloaddition (CuAAC) chemistry, and separation and visualizationof fragment-modified proteins by SDS-PAGE coupled with in-gelfluorescence scanning. Despite the structural simplicity and small sizeof the variable fragment groups, each probe produced marked anddifferential concentration-dependent protein labeling in HEK293T cells(FIG. 1C, FIG. 1E, and FIG. 1F). Negligible protein labeling wasobserved in the absence of UV light (FIG. 1C and FIG. 1E), exemplifyingthat the fragment-protein interactions correspond to reversible bindingevents that were converted to covalent adducts by photoreactivity.Exposure of cells to UV light from 5-60 min produced equivalent proteinlabeling (FIG. 1G), while washing cells prior to UV exposuresubstantially decrease FFF probe labeling for most, but not all proteins(FIG. 1H). Finally, a “fragment-less” probe bearing a methyl group (1)produced much less protein labeling, exemplifying that the variablegroup of FFF probes is critical for protein binding and further that 1serves as a useful control probe for the chemical proteomic mapping offragment-protein interactions in cells.

Example 27—a Global Analysis of Fragment-Protein Interactions in Cells

Fragment-binding proteins in human cells were globally mapped byquantitative chemical proteomics following the general protocol shown inFIG. 1A. Each FFF probe was initially compared to control probe 1 inpairwise experiments using isotopically light and heavy aminoacid-labeled HEK293T cells, where proteins strongly enriched by the testFFF probe over 1 (light:heavy ratios>5) were designated as test probetargets. Adhering to the general principles of FBLD, where a relativelysmall number of fragments are screened at high concentrations againstproteins, 11 FFF probes (2-4, 6, 8-9, 11-15) were analyzed at 200 μMeach (30 min incubation; n=2-3 per probe) in HEK293T cells, with asubset of probes also being evaluated in K562 cells. Under theseconditions, FFF probes displayed little to no cytotoxicity (FIG. 2K) andinteracted with an extensive array of proteins. To minimizefalse-positives, proteins were only designated as fragment targets ifthey were detected with at least three unique, quantifiable peptides andenriched (>five-fold over 1, FIG. 2L) by more than one FFF probe, or, ifenriched by only one probe, then required to be quantified in at leastthree independent experiments. Control experiments were also conductedwith representative probes to confirm that targets were enriched in aUV-dependent manner and showed SILAC ratios of ˜1.0 in experiments whereheavy and light cells were treated with equal concentrations of the sameFFF probe (FIG. 2M, FIG. 2N).

In aggregate, more than 2000 protein targets were identified for the FFFprobes, which individually displayed a broad range of proteinenrichments (FIG. 2A, FIG. 2O). When tested at lower concentrations (20μM), FFF probes enriched fewer protein targets (FIG. 2O, FIG. 2P),confirming that the extent of proteome engagement depends on probeconcentration. A review of expression-based proteomics data generated inHEK293T cells revealed that the protein targets of FFF probes spannedmore than five orders of magnitude in abundance and this range bracketedthe median protein abundance value in HEK293T cells (FIG. 2Q),exemplifying, along with other analyses (FIG. 2R, FIG. 2S), that FFFprobes enriched proteins across a broad range of expression.

To more quantitatively assess the structure-activity relationships(SARs) emerging from the initial FFF probe experiments, additionalstudies were performed comparing the relative protein interactionprofiles of FFF probes, wherein isotopically light and heavy cells weretreated with two different probes (probe-vs-probe comparisons) andprocessed as shown in FIG. 1A. These experiments exemplified thatproteins preferentially enriched by one FFF probe relative to another inprobe-vs-probe comparisons were also often preferentially enriched bythe same probe in original comparisons to control 1 (FIG. 2B-FIG. 2F).The probe-vs-probe comparisons also revealed that most of the proteinsshowing broad interaction potential across the fragment library inprobe-vs-control 1 experiments (light gray sub-bars, FIG. 2C) stillexhibited preferential interactions with one or a subset of FFF probes(FIG. 2G-FIG. 2J).

The fragment interactions profiles were verified for representativeproteins by recombinant expression in HEK293T cells. It was found thatthe fragment interaction profile for each recombinant protein, asmeasured by gel-based profiling (FIG. 1D), matched that of itsendogenous form as determined by quantitative MS-based proteomics, witheach target showing a strong preference for a distinct fragment probe(FIG. 2T, FIG. 2U).

Example 28—Types of Proteins and Protein Sites Targeted by Fragments

The fragment probes targeted both membrane and soluble proteins (FIG.3H), and only a small fraction (17%) of these proteins had known ligandsas estimated by their presence in the DrugBank database (FIG. 3A). Thissubset of previously liganded proteins was mainly enzymes (FIG. 3B). Incontrast, the much larger subset of fragment probe targets (83%) notrepresented in DrugBank showed a broader functional distribution, with areduced fractional representation of enzymes counterbalanced by expandedcoverage of channels/transporters/receptors, transcriptionfactors/regulators, and uncategorized proteins (FIG. 3B). A greaterpercentage of targets enriched by low (20 μM, 24%) versus high (200 μM,12%) concentrations of fragments were found in DrugBank (FIG. 3A),exemplifying that the capacity to screen higher concentrations offragment probes expanded the scope of newly discovered ligandableproteins in human cells.

Considering that the chemical proteomic results provided the firstevidence of ligandability for many protein targets, the fragment bindingsites on these proteins were aimed to be identified next. Determiningthe sites of photoreactive probe binding to proteins is technicallychallenging, but the simple structures of FFF probes, along with theimplementation of advanced chemical proteomic methods for isotopicallylabeling small-molecule probe-modified peptides is advantageous. Usingthese methods, over 800 unique peptides modified by one or more FFFprobes were identified that collectively derived from 443 proteins (FIG.3I and Tables 1-3) in HEK293T cells. Fragment-modified peptides werefound in both membrane and soluble proteins (FIG. 3I), and, while manyproteins were targeted by multiple FFF probes at the same site (FIG.3J), in the substantial majority of cases, only a singlefragment-modified peptide was identified per protein (FIG. 3C).

Using the pocket-detection algorithm fpocket, for the 186 proteinsharboring fragment-modified peptides for which crystal structures werealso available (FIG. 3I), it was found that the vast majority offragment-modified peptides (˜80%) overlapped directly and substantiallywith predicted ligand-binding pocket residues (FIG. 3D and FIG. 3K andTables 1-3). For proteins possessing multiple distinct fragment-modifiedpeptides, it was found that these peptides often mapped to a sharedpredicted pocket (FIG. 3L). For proteins with annotated functionalresidues (e.g., active site residues; 77 total proteins), approximately60% of the probe-modified peptides were within 6 angstroms of afunctional residue (FIG. 3M).

Many of the proteins with mapped fragment-binding sites and crystalstructures corresponded to enzymes (FIG. 3N), but non-enzymes of noteincluded: i) the 14-3-3 adapter protein YWHAE, which was modified byprobe 13 on a peptide (aa 197-215) that lines the primary interactioncleft for binding the oncoprotein myeloid leukaemia factor 1 (MLF1)(FIG. 3E); and ii) the proapoptotic effector protein BAX, which was alsomodified by probe 13 on a peptide (aa 66-79) within a groove that bindsthe BH3-domain containing activators Bim and Bid (FIG. 3F). Among theenzymes with mapped fragment-binding sites, the cysteine proteasecathepsin B (CTSB) was targeted by probe 9 at an active-site proximalpeptide (aa 315-332), and this interaction was blocked by the CTSBinhibitor Z-FA-FMK (FIG. 3G). Fragment-modified peptides at allostericor secondary ligand-binding sites were also identified, including, forinstance, a pocket on α-galactosidase (GLA) proposed to constitute asite for pharmacological chaperoning (FIG. 3O). Lastly, little overlap(<15%) was found between FFF targets and proteins liganded bycysteine-reactive electrophilic fragments (FIG. 3P). Even if thisanalysis was restricted to proteins that contained IA-reactive, theoverlap between FFF targets and electrophilic fragments targets remainedmodest (˜28%) (FIG. 3P). These results exemplify that reversible andirreversible fragments interact with largely distinct subsets of thehuman proteome.

Example 29—Functional Characterization of Fragment-Protein Interactions

FBLD typically identifies low-affinity (high μM to mM) hit compoundsthat often require substantial, structure-guided medicinal chemistryoptimization to improve potency and selectivity. As an alternative andcomplementary approach to structure-based ligand development, theproteome-wide, cell-based fragment screens are adapted to identifyhigher potency ligand-protein interactions. This goal is accomplished byscreening focused libraries of small molecules containing representativefragment cores elaborated with additional “binding” substituents forcompetitive blockade of FFF probe-protein interactions in cells (FIG.4A). Elaborated competitor molecules were purchased or synthesized forthree FFF probes—3, 6, and 8 (FIG. 4B and FIG. 4I-FIG. 4K)—and treatedcells with these competitors (17 total, each screened versus DMSO as acontrol) in eight-fold excess over the corresponding FFF probe (160 μMcompetitor, 20 μM FFF probe), after which FFF-modified proteins enrichedand identified as shown in FIG. 4A. A total of 100 competedtargets—defined as proteins that displayed substantial reductions(>3-fold) in signal in small-molecule competitor (heavy) versus DMSO(light) treated cells—were identified (FIG. 4C-FIG. 4F, FIG. 4L).Competed proteins showed widely varied SARs that ranged from broadinteractions with several (>5) competitors to preferential binding to asingle competitor (FIG. 4D).

Another 215 competed targets were mapped in experiments where a subsetof the competitors (five total) was tested against higher concentrationsof the corresponding FFF probes (200 μM) (FIG. 4M). A greaterrepresentation of DrugBank proteins was noted for competed targetsidentified with low (20 μM) versus high (200 μM) concentrations of FFFprobes (43% and 20%, respectively) (FIG. 4E). These results exemplifythat performing small-molecule competition studies with higherconcentrations of FFF probes, where a much greater proportion of probetargets are enriched and quantified (FIG. 2O), increases not only thetotal number of identified competed protein targets, but also thefraction of these targets that represent heretofore unliganded proteins.Finally, the competed protein targets exemplified a broad functionalclass distribution generally matching that found for the greatercollection of FFF targets (FIG. 4F), exemplifying that high-occupancysmall-molecule interactions were not biased toward a specific categoryof protein in human cells.

For determining if the discovered small-molecule ligands affectedprotein functions, one enzyme (PTGR2) and one transporter (SLC25A20)were selected for which distinct high-occupancy ligands were identifiedin competitor profiling experiments (FIG. 4G, FIG. 4H). These proteinsalso have important roles in human metabolism, but lack selective,cell-active inhibitors. Gel-based competitor profiling of recombinantPTGR2 and SLC25A20 (FIG. 5H) exemplified the preferential binding ofligands determined by MS-based proteomics (20 for PTGR2 and 21 forSLC25A20; FIG. 4G, FIG. 4H). Competitor molecules containing only thefragment head groups of FFF probes did not appreciably block probelabeling of PTGR2 and SLC25A20 (FIG. 5I). These results exemplify thatchemical proteomics discover weak fragment-protein interactions in cellsand, through competitive profiling of structurally elaborated fragmentanalogues, efficiently identify compounds that display superior proteinbinding.

PTGR2, or prostaglandin reductase 2, catalyzes the NADPH-dependentreduction of 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2 and regulatesadipogenesis through restricting 15-keto-PGE2 activity as a naturalligand for the nuclear receptor PPARγ. The only reported inhibitor ofPTGR2 is the NSAID drug indomethacin, which exhibits a very weak invitro IC50 value of ˜200 μM. Probe 8 modified two active site-proximalpeptides in PTGR2, and these reactions were sensitive to competition by20 (FIG. 5A), which also inhibited PTGR2-mediated reduction of15-keto-PGE2 with an IC50 value of 79 μM (FIG. 5B). A screen ofstructural analogues of 20 exemplified that substitution of the lactamring with a phenyl group and conversion of the piperidine core to apiperazine furnished 22 (FIG. 5C and FIG. 5J), which showedsubstantially increased potency (>20-fold) in assays measuring eithercompetition of 8-labeling (FIG. 5C) or 15-keto-PGE2 reductase activity(IC50=0.6 μM; FIG. 5B) of recombinant PTGR2. An inactive analogue 23 wasalso identified, which did not affect labeling of PTGR2 by 8 (FIG. 5Cand FIG. 5J) or PTGR2 catalytic activity (FIG. 5B).

Compound 22, but not 23, blocked FFF 8 labeling of endogenous PTGR2 inHEK293T cells with good potency (complete inhibition at 5 μM and ˜80%inhibition at 500 nM) and excellent selectivity (FIG. 5K-FIG. 5M). 22did not cross-react with ZADH2 (FIG. 5L), a sequence-related homologueof PTGR2 that was a principal off-target of 20 (FIG. 4G). Addition of 22also produced a concentration-dependent rescue of 15-keto-PGE2-dependentPPARγ transcriptional activity in cells recombinantly expressing PTGR2(FIG. 5D); in contrast, the inactive control compound 23 showed noeffect (FIG. 5D). Neither 22 nor 23 directly modulated PPARγ (FIG. 5N).The IC₅₀ value displayed by 22 for inhibition of PTGR2 in cells was ˜0.7μM (FIG. 5O), which meets the criterion for in situ activity of chemicalprobes put forth by the Structural Genomics Consortium.

SLC25A20 is a multi-pass transmembrane protein that transportslong-chain acylcarnitines into the mitochondrial matrix, where theselipids provide fatty acid substrates for β-oxidation. There are noselective small-molecule probes to study SLC25A20 function in humancells. The quantitative MS experiments exemplified SLC25A20 as a primarytarget of the elaborated coumarin-based competitor 21 (FIG. 4H), andthis interaction was confirmed for recombinant SLC25A20 in HEK293Tcells, where 21 blocked FFF probe 3 labeling of SLC25A20 with an IC₅₀ of˜10 μM (FIG. 5E). The coumarin-based compound 24 was identified as aninactive control (FIG. 5E, FIG. 5P, and FIG. 5Q).

Compound 21 (0.2-100 μM, 3 h), but not the inactive control 24 (100 μM),produced a strong, concentration-dependent increase in long-chain (C16,C18, C18:1) acylcarnitines in human squamous cell carcinoma (HSC5)cells, with significant effects being observed for 21 at concentrations(20-50 μM; FIG. 5F), where 21 also substantially blocked probe 3labeling of SLC25A20 in cells as measured by quantitative MS-basedproteomics (FIG. 5Q, FIG. 5R). No changes were found in short- ormedium-chain acylcarnitines (<C16), which are thought to cross themitochondrial membranes without conversion to acylcarnitine esters. HSC5cells treated with 21, but not 24 showed impaired capacity to oxidizepalmitate (FIG. 5G and FIG. 5S). These results exemplify that 21 acts asa selective, cell-active inhibitor of SLC25A20, leading to disruption ofmitochondrial long-chain acylcarnitine transport and FAO.

Example 30—Chemical Synthesis

Materials

Purchased starting materials were used as received unless otherwisenoted. All moisture sensitive reactions were performed in an inert, dryatmosphere of nitrogen in flame dried glassware. Reagent grade solventswere used for extractions and flash chromatography. All amines used inprobe library synthesis are available from commercial vendors. Allfragment-based competitors were synthesized or purchased through SigmaAldrich Market Select vendors. Reaction progress was checked byanalytical thin-layer chromatography (TLC, Merck silica gel 60 F-254plates). The plates were monitored either with UV illumination, or bycharring with anisaldehyde (2.5% p-anisaldehyde, 1% AcOH, 3.5% H₂SO₄(conc.) in 95% EtOH) or ninhydrin (0.3% ninhydrin (w/v), 97:3 EtOH-AcOH)stains. Flash column chromatography was performed using silica gel (F60,40-63 um, 60 A). Preparative thin layer chromotography (PTLC) wascarried out using glass backed PTLC plates 1000-2000 μm thickness(Analtech). The solvent compositions reported for all chromatographicseparations are on a volume/volume (v/v) basis. ¹H-NMR spectra wererecorded at either 400, 500 or 600 MHz and are reported in parts permillion (ppm) on the 6 scale relative to CDCl₃ (δ 7.26) as an internalstandard. Data are reported as follows: chemical shift, multiplicity(s=singlet, d=doublet, t=triplet, q=quartet, br=broad, m=multiplet),coupling constants (Hz), and integration. ¹³C-NMR spectra were recordedat either 100 or 125 MHz and are reported in parts per million (ppm) onthe δ scale relative to CDCl₃ (δ 77.00). Mass spectrometry data werecollected on a HP1100 single-quadrupole instrument (ESI; low resolution)or an Agilent ESI-TOF instrument (HRMS).

Synthesis of 3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid (30-3)

Ethyl 4-oxooct-7-ynoate (30-1) was synthesized following similarprocedures previously reported. A solution of crude pent-4-ynal (17.2 g,210 mmol) and ethyl acrylate (45.5 mL, 420 mmol, 2 equiv) in dioxane(250 mL) was added dropwise over a period of 4 h to a suspension ofthiazolium salt catalyst (7.88 g, 29.2 mmol, 0.14 equiv), triethylamine(20.4 mL, 147 mmol, 0.7 equiv) and ethyl acrylate (45.5 mL) in dioxane(300 mL) at 80° C. under an atmosphere of nitrogen. The mixture wasstirred and heated at 80° C. for 54 h and then volatiles removed byrotary evaporation. The residue was resuspended in methylene chloride(600 mL) and washed with aqueous 10% H₂SO₄ (150 mL), saturated aqueousNaHCO₃ (250 mL) and brine (250 mL), then dried over anhydrous Na₂SO₄ andvolatiles removed by rotary evaporation. Crude 30-1 was purified byflash column chromatography (100% hexanes→5%→10%→15%→20% ethyl acetatein hexanes), resulting in 30-1 as a light brown oil (10.7 g, 28%). ¹HNMR (400 MHz, CDCl₃) δ 4.20 (q, J=7.1, 2H), 2.86-2.76 (m, 4H), 2.68 (t,J=6.5, 2H), 2.54 (td, J=2.6, 7.3, 2H), 2.04 (t, J=2.7, 1H), 1.33 (td,J=2.2, 7.2, 4H). MS (ESI) calc'd for [M+H]+ C₁₀H₁₅O₃ ⁺ 183.1, found183.1.

4-Oxooct-7-ynoic acid (30-2). To a solution of 30-1 (9.46 g, 52 mmol) inmethanol (400 mL), added LiOH (6.2 g, 260 mmol, 5 equiv) and water (4.8mL, 267 mmol, 5.1 equiv) and let resulting solution stir at roomtemperature for 15 h when TLC (3:1 hexanes/ethyl acetate) indicated thecomplete consumption of starting material. The solution was carefullyacidified with aqueous HCl (6 M) until a pH of ˜3 was achieved. Theresulting solution was then extracted with methylene chloride and thecombined organic layers were dried over anhydrous Na₂SO₄ and volatileswere removed by rotary evaporation, resulting in 30-2 as a brown solid(7.6 g, 95%), which was used without further purification. ¹H NMR (400MHz, CDCl₃) δ 2.90-2.57 (m, 6H), 2.48 (td, J=2.5, 7.3, 2H), 1.98 (t,J=2.5, 1H). MS (ESI) calc'd for [M−H]− C₃H₉O₃ ⁻ 153.0, found 153.0.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid (30-3). A driedround bottom flask containing 30-2 (3.1 g, 20 mmol) cooled to 0° C. wascharged with 7N NH₃ in methanol (195 mL) and resulting solution wasstirred at 0° C. under an atmosphere of nitrogen for 3 h. At this time,a solution of hydroxylamine-O-sulfonic acid (3.2 g, 28.2 mmol, 1.4equiv) in anhydrous methanol (25 mL) was added dropwise via additionfunnel at 0° C. The resulting solution was stirred at 0° C. for anadditional 1 h and then allowed to warm to room temperature over 14 h.Resulting suspension was evaporated to dryness and resuspended inmethanol (30 mL) and solid was filtered and washed several times withmethanol. The combined filtrate was evaporated and resuspended inanhydrous methanol (180 mL), then cooled to 0° C. (protected fromlight). Diisopropylethylamine (7.8 mL) was added, followed by iodine(portion-wise), until a dark brown color persisted for more than 30 min,indicating total oxidation of diaziridine. The solution was then dilutedwith ethyl acetate (200 mL) and washed with aq. 1N HCl (200 mL),saturated aqueous Na₂S2O₃ (3×200 mL or until organic phase clarified)and brine. Combined aqueous phases were washed once with ethyl acetateand all organic layers were combined, then dried over anhydrous Na₂SO₄and volatiles removed by rotary evaporation. Crude 30-3 was purified byflash column chromatography (100% hexanes→2%→5%→10%→20% ethyl acetate inhexanes), resulting in 30-3 as a colorless oil (889 mg, 27%). ¹H NMR(400 MHz, CDCl₃) δ 2.18 (t, J=7.7, 2H), 2.06-1.98 (m, 3H), 1.81 (t,J=7.7, 2H), 1.66 (t, J=7.4, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 178.63,82.56, 69.37, 32.16, 28.21, 27.72, 27.46, 13.21. MS (ESI) calc'd for[M−H]− C₈H₉N₂O₂ ⁻ 165.1, found 165.1. Characterization matches thatpreviously reported by Li et al Angew Chem Int Ed. (2013) 52, 8551-6.

General Procedure 1: Coupling Procedure for the Synthesis of SimpleFragment-Based Probes

To a 4 mL vial containing3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid (30-3, 1 eq.) inDCM, commercially available amine (1.1 eq.), DIPEA (3.0 eq.) EDC-HCl(1.5 eq.), and HOBt (1.5 eq.) were added. Reaction mixtures were stirredat room temperature for 4 h to overnight when TLC indicated reactioncompleted. The crude samples were diluted with DCM and washed first withsaturated aqueous NH₄Cl (10 mL) and saturated aqueous NaHCO₃ (10 mL),then dried over anhydrous Na₂SO₄ and volatiles removed by rotaryevaporation. Crude products were purified by PTLC or flash columnchromatography.

General Procedure 2: Coupling Procedure for the Synthesis ofPhotoaffinity Probe Library Used in Phenotypic Screening

A 4 mL vial was charged with3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanoic acid (10 mg, 0.060 mmol)or propionic acid (0.060 mmol), commercially available amine (0.060mmol, 1 eq.), DIPEA (0.032 mL, 0.181 mmol, 3.0 eq.), HATU (34.3 mg,0.090 mmol, 1.5 eq.) and DMF (1 mL). Reaction mixtures were stirred atroom temperature for 4 h. The crude samples were diluted with methanolto a total volume of 1.6 mL then purified by reverse phase HPLC usingfollowing conditions:

LC/MS conditions for Library Characterization Column Xbridge Prep C18 19× 150 mm, 10 μm Flow Rate 15 ml/min Mobile Phase A 10 mM ammoniumacetate in water Mobile Phase B Acetonitrile Gradient 10% B to 100% Bover 20 min followed by a 3 min wash at 100% B and 2 min equilibrationat 10% B.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-methylpropanamide (1) GeneralProcedure 1. Purified by SiO₂ flash chromatography (Hexane/EtOAc,7:3→1:1) to afford 1 as a colorless sticky solid (6 mg, 93%). ¹H NMR(400 MHz, CDCl₃) δ 5.56 (brs, 1H), 2.82 (d, J=2.2 Hz, 2H), 2.08-1.98 (m,3H), 1.94 (m, 2H), 1.90-1.83 (m, 2H), 1.66 (t, J=7.4 Hz, 2H). ¹³C NMR(126 MHz, CDCl₃) δ 172.12, 83.09, 69.57, 32.79, 30.58, 28.83, 28.25,26.80, 13.68. HRMS (ESI-TOF) calcd for C₉H₁₄N₃O 180.1131 (M+H⁺), found180.1131.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanamide(2) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 2 as a white sticky solid (22 mg, 76%). ¹HNMR (400 MHz, CDCl₃) δ 9.18 (s, 1H), 7.56-7.30 (m, 8H), 7.22-7.10 (m,2H), 5.53 (d, J=7.9 Hz, 1H), 2.29-2.13 (m, 2H), 2.07-1.97 (m, 3H), 1.87(t, J=7.4 Hz, 2H), 1.68 (t, J=7.4 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ171.34, 168.74, 138.54, 137.36, 132.21, 131.45, 130.69, 129.87, 128.25,127.61, 124.18, 121.46, 82.76, 69.26, 67.13, 32.30, 30.37, 28.30, 27.87,13.33. HRMS (ESI-TOF) calcd for C₂₃H₂₂N₅O₂ 400.1768 (M+H⁺), found400.1768.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-(2-oxo-2H-chromen-6-yl)propanamide(3) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:2) to afford 3 as a yellow sticky solid (12.8 mg, 57%).¹H NMR (400 MHz, CDCl₃) δ 8.01 (d, J=2.2 Hz, 1H), 7.69 (d, J=9.6 Hz,1H), 7.62 (br s, 1H), 7.42 (dd, J=8.9, 2.5 Hz, 1H), 7.29 (d, 7.7 Hz,1H), 6.44 (d, J=9.6 Hz, 1H), 2.16 (t, J=7.5 Hz, 2H), 2.04 (td, J=7.4,2.6 Hz, 2H), 2.01-1.92 (m, 3H), 1.75 δ 1.62 (m, 2H). ¹³C NMR (101 MHz,CDCl₃) δ 169.69, 160.82, 150.48, 143.49, 134.28, 123.57, 119.04, 118.58,117.20, 82.67, 69.33, 32.44, 31.16, 28.09, 27.80, 13.29. HRMS (ESI-TOF)calcd for C₁₇H₁₆N₃O₃ 310.1186 (M+H⁺), found 310.1186.

N-(Benzo[b]thiophen-5-ylmethyl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(4) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 4 as a off-white sticky solid (12.3 mg,44%). ¹H NMR (500 MHz, CDCl₃) δ 7.84 (d, J=8.3 Hz, 1H), 7.73 (s, 1H),7.46 (d, J=5.4 Hz, 1H), 7.30 (d, J=5.4 Hz, 1H), 7.26 (d, J=8.0 Hz, 1H),5.80 (br s, 1H), 4.54 (d, J=5.7 Hz, 2H), 2.03-1.95 (m, 5H), 1.91 δ 1.86(m, 2H), 1.64 (t, J=7.5 Hz, 2H). ¹³C NMR (126 MHz, CDCl₃) δ 171.27,140.32, 139.41, 134.65, 127.61, 124.71, 124.06, 123.22, 83.10, 69.62,44.23, 32.82, 30.73, 28.75, 13.70. HRMS (ESI-TOF) calcd for C₁₇H₁₈N₃OS312.1165 (M+H⁺), found 312.1167

N-(Benzofuran-5-ylmethyl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(5) General Procedure 1. Purified by PTLC (Hexane/EtOAc, 3:1) to afford5 as a off-white sticky solid (10.8 mg, 76%). ¹H NMR (400 MHz, CDCl₃) δ7.63 (d, J=2.2 Hz, 1H), 7.54-7.49 (m, 1H), 7.46 (d, J=8.5 Hz, 1H), 7.21(dd, J=8.5, 1.8 Hz, 1H), 6.74 (dd, J=2.2, 1.0 Hz, 1H), 5.75 (brs, 1H),4.51 (d, J=5.7 Hz, 2H), 2.06-1.83 (m, 7H), 1.65 (t, J=7.4 Hz, 2H). HRMS(ESI-TOF) calcd for C₁₇H₁₈N₃O₂ 296.1393 (M+H⁺), found 296.1392

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)propanamide(6) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 6 as a light brown sticky solid (33 mg,56%). ¹H NMR (500 MHz, CDCl₃) δ 7.43 (d, 2.4 Hz, 1H), 7.35 (brs, 1H),7.29 (dd, J=8.7, 2.5 Hz, 1H), 6.91 (d, J=8.7 Hz, 1H), 3.33 (s, 3H),2.99-2.89 (m, 2H), 2.76-2.65 (m, 2H), 2.19 (t, J=7.5, 6.7 Hz, 2H), 2.12(td, J=7.4, 2.6 Hz, 2H), 2.07 (t, J=2.6 Hz, 1H), 2.02 (t, J=7.5 Hz, 2H),1.76 (t, J=7.5 Hz, 2H). ¹³C NMR (126 MHz, CDCl₃) δ 170.59, 169.79,137.62, 133.17, 127.38, 120.28, 119.32, 115.38, 83.09, 69.69, 32.87,31.99, 31.58, 29.98, 28.61, 28.23, 25.88, 13.71. HRMS (ESI-TOF) calcdfor C₁₈H₂₁N₄O₂ 325.1659 (M+H⁺), found 325.1658

N-((1H-Indol-5-yl)methyl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(7) General Procedure 1. Purified by PTLC (Hexane/EtOAc, 3:1) to afford7 as an off-white sticky solid (12.2 mg, 57%). ¹H NMR (500 MHz, CDCl₃) δ8.31 (brs, 1H), 7.57-7.50 (m, 1H), 7.36 (d, J=8.3 Hz, 1H), 7.22 (dd,J=3.2, 2.4 Hz, 1H), 7.11 (dd, J=8.3, 1.7 Hz, 1H), 6.53-6.51 (m, 1H),5.71 (brs, 1H), 4.50 (d, J=5.4 Hz, 2H), 2.00 (td, J=7.4, 2.6 Hz, 2H),1.98-1.92 (m, 3H), 1.89-1.84 (m, 2H), 1.64 (t, J=7.4 Hz, 2H). ¹³C NMR(126 MHz, CDCl₃) δ 171.11, 135.68, 129.70, 128.47, 125.34, 122.74,120.65, 111.79, 102.96, 83.14, 69.61, 44.83, 32.78, 30.79, 28.86, 13.70.HRMS (ESI-TOF) calcd for C₁₇H₁₉N₄O 295.1553 (M+H⁺), found 295.1555.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-1-(4-phenylpiperidin-1-yl)propan-1-one(8) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 8 as an off-white sticky solid (19.7 mg,88%). ¹H NMR (400 MHz, CDCl₃) δ 7.31 (t, J=7.5 Hz, 2H), 7.25-7.16 (m,3H), 4.85-4.69 (m, 1H), 3.92-3.83 (m, 1H), 3.10 (apparent td, J=13.3,2.7 Hz, 1H), 2.73 (apparent tt, J=12.2, 3.7 Hz, 1H), 3.62 (apparent td,J=13.3, 2.8 Hz, 1H), 2.13-2.08 (m, 2H), 2.05 (td, J=7.5, 2.7 Hz, 2H),1.98 (t, J=2.6 Hz, 1H), 1.92-1.84 (m, 2H), 1.69 (t, J=7.5 Hz, 2H)(rotomeric isomers present). ¹³C NMR (101 MHz, CDCl₃) δ 169.33, 145.08,128.59, 126.70, 126.54, 82.80, 69.12, 46.09, 42.75, 42.55, 33.81, 32.80,32.57, 28.08, 26.99, 13.34. HRMS (ESI-TOF) calcd for C₁₉H₂₃N₃O 310.1914(M+H⁺), found 310.1916.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-(4-(piperidin-4-yl)phenyl)propanamide(9) Followed General Procedure 1 for amide bond coupling. Crude 9 wasthen re-dissolved in DCM (1 mL) and TFA (0.3 mL) was carefully added.The resulting mixture was evaporated and crude 9 was purified by PTLC(DCM/MeOH, 6:1) yielding 9 as a white solid (22 mg, 67%, 2 steps). ¹HNMR (500 MHz, CDCl₃) δ 7.44 (d, J=8.1 Hz, 2H), 7.18 (d, J=8.2 Hz, 2H),7.13 (s, 1H), 3.45 (d, J=12.7 Hz, 2H), 3.00-2.89 (m, 2H), 2.76-2.65 (m,3H), 2.12 (t, J=7.5 Hz, 2H), 2.04 (td, J=7.5, 2.6 Hz, 2H), 2.02-1.91 (m,3H), 1.68 (t, J=7.4 Hz, 2H). HRMS (ESI-TOF) calcd for C₁₉H₂₅N₄O 325.2023(M+H⁺), found 325.2023.

N-([1,1′-Biphenyl]-4-ylmethyl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(10) General Procedure 1. Purified by PTLC (Hexane/EtOAc, 4:1) to afford10 as a white sticky solid (18.5 mg, 78%). ¹H NMR (400 MHz, CDCl₃) δ7.61-7.52 (m, 4H), 7.44 (t, J=7.5 Hz, 2H), 7.38-7.33 (m, 4H), 5.77 (brs, 1H), 4.47 (d, J=5.7 Hz, 2H), 2.09-1.94 (m, 5H), 1.94-1.85 (m, 2H),1.66 (t, J=7.4 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 170.92, 140.63,137.05, 128.80, 128.32, 127.48, 127.39, 127.06, 82.70, 69.22, 43.47,32.42, 30.32, 28.34, 27.86, 13.31. HRMS (ESI-TOF) calcd for C₂₁H₂₂N₃O332.1757 (M+H⁺), found 332.1755.

1-(4-Benzhydrylpiperazin-1-yl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propan-1-one(11) General Procedure 1. Purified by PTLC (DCM/MeOH, 20:1) to afford 11as an off-white sticky residue (12 mg, 75%). ¹H NMR (500 MHz, CDCl₃) δ7.43-7.38 (m, 4H), 7.31-7.24 (m, 4H), 7.22-7.16 (m, 2H), 4.23 (s, 1H),3.66-3.54 (m, 2H), 3.48-3.34 (m, 2H), 2.36 (apparent t, J=5.0 Hz, 4H),2.06-1.98 (m, 4H), 1.96 (t, J=2.7 Hz, 1H), 1.85-1.80 (m, 2H), 1.65 (t,J=7.4 Hz, 2H). ¹³C NMR (126 MHz, CDCl₃) δ 169.84, 142.47, 129.01,128.25, 127.58, 69.52, 52.34, 51.93, 45.96, 42.33, 32.93, 28.41, 27.22,13.71. HRMS (ESI-TOF) calcd for C₂₅H₂₉N₄O 401.2336 (M+H⁺), found401.2335.

3-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)propanamide(12) General Procedure 1. Purified by PTLC (DCM/MeOH, 9:1) to afford 12as an off-white sticky solid (16 mg, 76%). ¹H NMR (500 MHz, CDCl₃) δ7.51 (s, 1H), 7.45 (d, J=8.1 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 3.47 (s,2H), 2.36 (s, 3H), 2.12 (t, J=7.5 Hz, 2H), 2.02 (td, J=7.4, 2.7 Hz, 2H),1.98 (t, J=2.6 Hz, 1H), 1.92 (t, J=7.5 Hz, 2H), 1.67 (t, J=7.4 Hz, 2H).¹³C NMR (126 MHz, CDCl₃) δ 169.83, 137.24, 130.20, 120.29, 83.11, 62.59,55.21, 52.68, 45.93, 32.84, 31.64, 28.63, 28.26, 13.71. HRMS (ESI-TOF)calcd for C₂₀H₂₈N₅O 354.2288 (M+H⁺), found 354.2289.

1-(2-Benzylpiperidin-1-yl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propan-1-one(13) ¹H NMR (500 MHz, CDCl₃) General Procedure 1. Purified by PTLC(Hexane/EtOAc, 1:1) to afford 13 as an off-white sticky solid (9 mg,77%). δ 7.35-7.15 (m, 3H), 7.11 (apparent d, J=7.4 Hz, 2H), 5.14-4.95(m, 0.5H), 4.68-4.57 (m, 0.5H), 4.13-3.97 (m, 0.5H), 3.63-3.50 (m,0.5H), 3.21-3.02 (m, 1H), 2.89-2.69 (m, 2H), 2.09-1.87 (m, 4H),1.83-1.24 (m, 11H). ¹³C NMR (126 MHz, CDCl₃) δ 169.99, 139.08, 139.01,129.61, 129.46, 129.19, 128.73, 127.17, 126.63, 83.19, 69.49, 69.42,55.55, 50.01, 41.70, 37.16, 37.04, 36.10, 32.88, 32.70, 29.92, 28.49,28.46, 28.18, 27.78, 26.86, 26.47, 26.45, 25.89, 19.67, 19.27, 13.72,13.70. Note: rotomeric isomers observed. HRMS (ESI-TOF) calcd forC₂₀H₂₆N₃O 324.2070 (M+H⁺), found 324.2068.

N-((3s,5s,7s)-Adamantan-1-yl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(14) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 10:1→6:1→3:1) to afford 14 as a colorless sticky solid(14.7 mg, 68%). ¹H NMR (500 MHz, CDCl₃) δ 5.08 (brs, 1H), 2.15 (m, 3H),2.04-1.95 (m, 9H), 1.88-1.75 (m, 4H), 1.72-1.59 (m, 8H). ¹³C NMR (126MHz, CDCl₃) δ 170.46, 83.17, 69.52, 52.41, 42.02, 36.74, 32.89, 31.69,29.86, 29.84, 28.73, 13.71. HRMS (ESI-TOF) calcd for C₂₈H₂₆N₃O 300.2070(M+H⁺), found 300.2067.

N-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamide(15) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 15 as a white solid (20.2 mg, 71%). ¹H NMR(500 MHz, CDCl₃) δ 6.74 (d, J=7.9 Hz, 1H), 6.67 (d, J=1.7 Hz, 1H), 6.62(dd, J=7.9, 1.7 Hz, 1H), 5.93 (s, 2H), 5.43 (d, J=7.4 Hz, 1H), 3.45 (td,J=6.9, 5.8 Hz, 2H), 2.72 (t, J=6.9 Hz, 2H), 2.01 (td, J=7.4, 2.7 Hz,2H), 1.96 (t, J=2.6 Hz, 1H), 1.90 δ 1.78 (m, 4H), 1.62 (t, J=7.4 Hz,2H). ¹³C NMR (126 MHz, CDCl₃) δ 171.37, 148.27, 146.65, 132.85, 122.01,109.43, 108.79, 101.34, 83.10, 69.59, 41.21, 35.71, 32.81, 30.74, 28.72,13.69. HRMS (ESI-TOF) calcd for C₁₇H₂₀N₃O₃ 314.1499 (M+H⁺), found314.1500.

(S)-2-(3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)propanamido)-4-methyl-N-(naphthalen-2-yl)pentanamide(25) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:1) to afford 25 as a white solid (27 mg, 53%). ¹H NMR(500 MHz, CDCl₃) δ 9.39 (s, 1H), 8.20 (d, J=2.2 Hz, 1H), 7.70-7.63 (m,1H), 7.63-7.54 (m, 2H), 7.41 (dd, J=8.8, 2.1 Hz, 1H), 7.37-7.30 (m, 2H),6.94 (d, J=7.9 Hz, 1H), 4.80 (td, J=8.3, 5.6 Hz, 1H), 2.09-1.94 (m, 2H),1.93 (t, J=2.6 Hz, 1H), 1.91-1.70 (m, 7H), 1.51 (t, J=7.4 Hz, 2H), 1.00(dd, J=12.9, 6.1 Hz, 6H). ¹³C NMR (125 MHz, CDCl₃) δ 172.64, 171.84,135.71, 134.08, 131.04, 129.03, 128.02, 126.74, 125.37, 120.43, 117.39,83.02, 69.65, 53.48, 41.31, 32.56, 30.42, 28.65, 28.13, 25.35, 23.40,22.59, 13.59. HRMS (ESI-TOF) calcd for C₂₄H₂₉N₄O₂ 405.2285 (M+H⁺), found405.2285

(S)-3-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)-N-(1-((4-methoxynaphthalen-2-yl)amino)-1-oxopropan-2-yl)propanamide(26) General Procedure 1. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 9:1→4:1→2:1) to afford 26 as a white solid (147 mg, 73%).¹H NMR (500 MHz, CDCl₃) δ 8.86 (s, 1H), 8.29-8.14 (m, 1H), 7.79-7.63 (m,2H), 7.50 (ddd, J=8.2, 6.7, 1.4 Hz, 1H), 7.44 (ddd, J=8.2, 6.8, 1.3 Hz,1H), 7.17 (d, J=1.8 Hz, 1H), 6.39 (d, J=7.5 Hz, 1H), 4.83 (p, J=7.1 Hz,1H), 4.02 (s, 3H), 2.21-2.03 (m, 5H), 2.02-1.93 (m, 2H), 1.71 (t, J=7.2Hz, 2H), 1.61 (d, J=7.0 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 172.31,171.22, 156.39, 136.00, 134.77, 127.54, 124.74, 123.51, 122.22, 109.59,99.18, 82.97, 69.77, 55.92, 50.34, 32.66, 30.70, 28.76, 28.18, 18.39,13.62. HRMS (ESI-TOF) calcd for C₂₂H₂₅N₄O₃ 393.1921 (M+H⁺), found393.1923

General Procedure 3:

To a solution of N-butanoyl-L-leucine (Effenberger et al., 2015) (1equiv) in DCM (0.06M relative to acid), added commercially availableamine (1.1 equiv), DIPEA (2.2 equiv) EDC-HCl (1.2 equiv) and HOBt (1.2equiv) were added. Reaction mixtures were stirred at room temperaturefor 4 h to overnight when TLC indicated reaction completed. The crudesamples were diluted with DCM and washed first with saturated aqueousNH₄Cl and saturated aqueous NaHCO₃, then dried over anhydrous Na₂SO₄ andvolatiles removed by rotary evaporation. Crude products were purified byPTLC or flash column chromatography.

(S)-2-butyramido-4-methyl-N—((S)-1,2,3,4-tetrahydronaphthalen-1-yl)pentanamide(29) General Procedure 3. Purified by PTLC (Hexane/EtOAc, 1:1) to afford29 as an off-white solid (24 mg, 73%). ¹H NMR (400 MHz, CDCl₃) δ7.23-7.04 (m, 4H), 6.39 (d, J=8.8 Hz, 1H), 5.99 (d, J=8.3 Hz, 1H),5.16-5.08 (m, 1H), 4.44 (td, J=8.4, 5.4 Hz, 1H), 2.77 (qd, J=16.9, 8.7Hz, 2H), 2.16 (td, J=7.3, 1.4 Hz, 2H), 2.08-1.93 (m, 1H), 1.91-1.39 (m,8H), 1.03-0.81 (m, 9H). ¹³C NMR (125 MHz, CDCl₃) δ 173.37, 171.79,137.83, 136.59, 129.52, 128.83, 127.71, 126.68, 52.03, 48.02, 41.91,38.87, 30.49, 29.59, 25.28, 23.27, 22.76, 20.46, 19.48, 14.09. HRMS(ESI-TOF) calcd for C₂₀H₃₁N₂O₂ 331.2380 (M+H⁺), found 331.2383

(S)—N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-butyramido-4-methylpentanamide(30) General Procedure 3. Purified by SiO₂ flash chromatography(Hexane/EtOAc, 3:2) to afford 30 as a white solid (181 mg, 75%). ¹H NMR(500 MHz, CDCl₃) δ 6.73 (d, J=7.9 Hz, 1H), 6.69-6.64 (m, 1H), 6.62 (dd,J=7.9, 1.7 Hz, 1H), 6.45-6.34 (m, 1H), 6.06 (t, J=7.9 Hz, 1H), 5.92 (s,2H), 4.39 (td, J=8.3, 6.1 Hz, 1H), 3.49 (dq, J=13.5, 6.9 Hz, 1H), 3.38(dq, J=13.3, 6.8 Hz, 1H), 2.71 (t, J=7.1 Hz, 2H), 2.15 (t, J=7.5 Hz,2H), 1.70-1.41 (m, 5H), 0.97-0.85 (m, 9H). ¹³C NMR (125 MHz, CDCl₃) δ173.43, 172.46, 148.18, 146.60, 132.80, 122.02, 109.46, 108.72, 101.29,51.89, 41.55, 41.20, 38.82, 35.70, 25.18, 23.17, 22.69, 19.44, 14.08.HRMS (ESI-TOF) calcd for C₁₉H₂₉N₂O₄ 349.2122 (M+H⁺), found 349.2124

General Procedure 4:

To commercially available amine (1.0 equiv) in DCM (0.1 M), added DIPEA(1.1 equiv) followed by the slow addition of butanoyl chloride (1.0equiv). Resulting mixture was allowed to stir at room temperature untilamine was fully consumed, as indicated by TLC. The crude mixture wasdiluted with DCM, washed first with saturated aqueous NH₄Cl andsaturated aqueous NaHCO₃, then dried over anhydrous Na₂SO₄ and volatilesremoved by rotary evaporation. Crude products were purified by PTLC.

(S)-2-butyramido-4-methyl-N-(naphthalen-2-yl)pentanamide (27) GeneralProcedure 4. Purified by PTLC (DCM/MeOH, 20:1) to afford 27 as a whitesolid (15 mg, 58%). ¹H NMR (400 MHz, CDCl₃) δ 9.41 (s, 1H), 8.26-8.09(m, 1H), 7.69-7.54 (m, 3H), 7.42 (dd, J=8.8, 2.1 Hz, 1H), 7.38-7.29 (m,J=7.1, 3.5 Hz, 2H), 6.62 (d, J=8.0 Hz, 1H), 4.83 (td, J=8.3, 5.9 Hz,1H), 2.22 (apparent td, J=7.3, 2.9 Hz, 2H), 1.92-1.57 (m, 5H), 0.99 (dd,J=12.4, 6.1 Hz, 6H), 0.90 (t, J=7.4 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ174.40, 171.36, 135.78, 134.13, 131.00, 128.96, 128.00, 127.85, 126.69,125.26, 120.40, 117.15, 53.08, 40.96, 38.78, 25.33, 23.34, 22.67, 19.53,14.04. HRMS (ESI-TOF) calcd for C₂₀H₂₆N₂O₂ 327.2067 (M+H⁺), found327.2069

(S)—N-(1-((4-methoxynaphthalen-2-yl)amino)-1-oxopropan-2-yl)butyramide(28) General Procedure 4. Purified by PTLC (DCM/MeOH, 9:1) to afford 28as a colorless solid (22.7 mg, 68%). ¹H NMR (500 MHz, CDCl₃) δ 9.36 (s,1H), 8.12 (dd, J=8.2, 1.4 Hz, 1H), 7.69-7.64 (m, 1H), 7.62 (d, J=8.1 Hz,1H), 7.40 (ddd, J=8.2, 6.7, 1.4 Hz, 1H), 7.34 (ddd, J=8.2, 6.8, 1.3 Hz,1H), 7.10 (d, J=1.8 Hz, 1H), 6.56 (d, J=7.5 Hz, 1H), 4.91 (p, J=7.1 Hz,1H), 3.91 (s, 3H), 2.27 (apparent td, J=7.4, 3.1 Hz, 2H), 1.78-1.68 (m,2H), 1.55 (d, J=6.9 Hz, 3H), 0.96 (t, J=7.4 Hz, 3H). ¹³C NMR (125 MHz,CDCl₃) δ 173.23, 170.49, 155.47, 135.40, 133.97, 126.67, 123.75, 122.56,121.34, 108.54, 98.25, 55.04, 49.29, 38.06, 18.74, 17.78, 13.23. HRMS(ESI-TOF) calcd for C₁₈H₂₃N₂O₃ 315.1703 (M+H⁺), found 315.1703

1-(4-phenylpiperidin-1-yl)butan-1-one (49) General Procedure 4. Purifiedby SiO₂ flash chromatography (Hexanes/EtOAc, 10:1→3:1) to afford 49 as awhite solid (110 mg, 77%). ¹H NMR (500 MHz, CDCl₃) δ 7.31 (t, J=7.6 Hz,2H), 7.24-7.16 (m, 3H), 4.81 (ddd, J=13.5, 4.2, 2.2 Hz, 1H), 3.99 (ddt,J=13.8, 4.2, 2.2 Hz, 1H), 3.12 (td, J=13.1, 2.6 Hz, 1H), 2.73 (tt,J=12.2, 3.7 Hz, 1H), 2.68-2.56 (m, 1H), 2.44-2.25 (m, 2H), 2.00-1.83 (m,2H), 1.75-1.52 (m, 4H), 0.99 (t, J=7.4 Hz, 3H). HRMS (ESI-TOF) calcd forC₁₃H₁₄NO₃ 232.0968 [M+H⁺], found 232.0967

N-(2-oxo-2H-chromen-6-yl)butyramide (50) General Procedure 4. Purifiedby SiO₂ flash chromatography (Hexanes/EtOAc, 10:1→3:1) to afford 50 as alight yellow solid (116 mg, 81%). ¹H NMR (400 MHz, CDCl₃) δ 8.07 (d,J=2.5 Hz, 1H), 7.69 (d, J=9.5 Hz, 1H), 7.52 (brs, 1H), 7.42 (dd, J=8.9,2.6 Hz, 1H), 7.28 (d, J=2.4 Hz, 1H), 6.44 (d, J=9.6 Hz, 1H), 2.39 (t,J=7.4 Hz, 2H), 1.79 (h, J=7.4 Hz, 2H), 1.03 (t, J=7.4 Hz, 3H). HRMS(ESI-TOF) calcd for C₁₅H₂₂NO 232.1696 [M+H⁺], found 232.1696

1-(4-(2-Methoxyphenyl)piperazin-1-yl)-2-phenylethan-1-one (22). To amixture of 1-(2-methoxyphenyl)piperazine (30 mg, 0.156 mmol) inanhydrous CH₂Cl₂ (1.5 mL) and pyridine (0.5 mL) was addedphenylacetylchloride (23 mg, 0.172 mmol, 1.1 equiv). The reactionmixture was stirred at room temperature for 12 h before removing thesolvent under reduced pressure. The remaining residue was purified byPTLC (Hexanes/EtOAc, 2/1) providing the title compound 22 as a colorlessoil (46 mg, 96%). ¹H NMR (600 MHz, CDCl₃) δ 7.33 (t, J=7.5 Hz, 2H),7.29-7.22 (m, 3H), 7.02 (td, J=7.7, 1.5 Hz, 1H), 6.93-6.81 (m, 3H),3.85-3.83 (m, 5H), 3.79 (s, 2H), 3.64-3.59 (m, 2H), 3.00 (t, J=5.1 Hz,2H), 2.85 (t, J=5.0 Hz, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 40.66, 41.58,46.00, 50.02, 50.37, 54.99, 110.86, 117.95, 120.58, 123.08, 126.39,128.16, 128.33, 134.67, 140.20, 151.78, 169.08. HRMS (ESI-TOF) calcd forC₁₉H₂₃N₂O₂ 311.1754 [M+H⁺], found 311.1753

1-(Benzylsulfonyl)-4-(2-methoxyphenyl)piperidine (23). To a mixture of4-(2-methoxyphenyl)piperidine (50 mg, 0.26 mmol) andN,N-diisopropylethylamine (DIPEA, 0.100 mL, 0.58 mmol) in anhydrous THF(3.0 mL) was added benzylsulfonyl chloride (55 mg, 0.28 mmol, 1.1equiv.) under N₂. The reaction mixture was stirred at 50° C. for 12 h.The reaction mixture was poured into a separatory funnel with brine (10mL) and extracted with EtOAc (2×10 mL). The combined organic layers werethen dried over anhydrous Na₂SO₄ and concentrated under reducedpressure. The remaining residue was purified by SiO₂ flashchromatography (Hexanes/EtOAc, 5/1) providing the title compound 23 as aslightly beige powder (50 mg, 56%). ¹H NMR (600 MHz, CDCl₃) δ 7.46-7.35(m, 5H), 7.19 (ddd, J=8.3, 7.4, 1.7 Hz, 1H), 7.10 (dd, J=7.6, 1.7 Hz,1H), 6.93 (td, J=7.5, 1.1 Hz, 1H), 6.85 (dd, J=8.2, 1.1 Hz, 1H), 4.24(s, 2H), 3.83-3.75 (m, 5H), 2.96 (tt, J=12.1, 3.5 Hz, 1H), 2.72 (td,J=12.4, 2.5 Hz, 2H), 1.80-1.73 (m, 2H), 1.64 (qd, J=12.6, 4.2 Hz, 2H).¹³C NMR (151 MHz, CDCl₃) δ 169.48, 152.18, 140.60, 135.07, 128.73,128.56, 126.79, 123.48, 120.98, 118.35, 111.26, 55.39, 50.77, 50.42,46.40, 41.98, 41.06. HRMS (ESI-TOF) calcd for C₁₉H₂₄NO₃S 346.1471(M+H⁺), found 346.1472.

N-(2-(4-(2-methoxyphenyl)piperidin-1-yl)-2-oxoethyl)acetamide (51).4-(2-methoxyphenyl)piperidine (50 mg, 0.26 mmol), acetylglycine (46 mg,0.39 mmol, 1.5 equiv.) and N,N-diisopropylethylamine (DIPEA, 0.137 mL,0.58 mmol, 3.0 equiv.) in anhydrous DMF (1.0 mL) were added EDC (75 mg,0.39 mmol, 1.5 equiv.) and HOAt (53 mg, 0.39 mmol, 1.5 equiv.). Thereaction mixture was stirred at room temperature for ˜12 h beforeremoving the solvent under reduced pressure. The remaining residue waspurified by PTLC (CH₂Cl₂/MeOH, 9/1) providing the title compound 51 as acolorless oil (40 mg, 53%). ¹H NMR (600 MHz, CDCl₃) δ 7.21 (ddd, J=8.2,7.4, 1.7 Hz, 1H), 7.10 (dd, J=7.6, 1.8 Hz, 1H), 6.93 (td, J=7.5, 1.1 Hz,1H), 6.87 (dd, J=8.2, 1.1 Hz, 1H), 6.67 (brs, 1H), 4.77-4.71 (m, 1H),4.16-4.09 (m, 1H), 4.05 (dd, J=17.3, 3.8 Hz, 1H), 3.83-3.81 (m, 4H),3.24-3.12 (m, 2H), 2.75 (td, J=12.9, 2.8 Hz, 1H), 2.05 (s, 3H),1.94-1.85 (m, 2H), 1.68-1.52 (m, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 23.07,31.26, 32.12, 35.43, 41.40, 43.13, 45.30, 55.28, 110.42, 120.70, 126.38,127.40, 132.74, 156.66, 166.03, 170.09. HRMS (ESI-TOF) calcd forC₁₆H₂₃N₂O₃ 291.1703 (M+H⁺), found 291.1704.

1-(4-(2-Methoxyphenyl)piperidin-1-yl)-2-(piperidin-1-yl)ethan-1-one(52). To a mixture of 4-(2-methoxyphenyl)piperidine (350 mg, 1.83 mmol)and triethylamine (0.643 mL, 4.57 mmol, 2.5 equiv.) in anhydrous CH₂Cl₂(3.5 mL) was slowly added chloroacetyl chloride (0.175 mL, 2.20 mmol,1.2 equiv.) under N₂ at 0° C. The reaction mixture was stirred at roomtemperature for 1 h and diluted with EtOAc (10 mL). The mixture waswashed with 1N aqueous HCl (1×10 mL) and brine. The organic layer wasthen dried over anhydrous Na₂SO₄ and concentrated under reduced pressureto afford a crude compound as a dark brown oil which was used to nextreaction without further purification.

To a mixture of the oil (100 mg, 0.37 mmol) and triethylamine (0.156 mL,1.12 mmol, 3.0 equiv.) in CH₃CN (1 mL) was added piperidine (0.110 mL,1.12 mmol, 3.0 equiv.) under N₂. The reaction mixture was stirred atroom temperature for 1 h and then quenched with H₂O (1 mL). The productwas extracted with EtOAc (2×10 mL). The combined organic layers werethen dried over anhydrous Na₂SO₄ and concentrated under reducedpressure. The remaining residue was purified by SiO₂ flashchromatography (Hexanes/EtOAc, 3/1, 3% Et₃N) providing the titlecompound 52 as a pale yellow oil (84 mg, 71% in 2 steps). ¹H NMR (600MHz, CDCl₃) δ 7.20 (ddd, J=8.2, 7.4, 1.7 Hz, 1H), 7.12 (dd, J=7.6, 1.7Hz, 1H), 6.93 (td, J=7.5, 1.2 Hz, 1H), 6.87 (dd, J=8.2, 1.1 Hz, 1H),4.77-4.70 (m, 1H), 4.32-4.25 (m, 1H), 3.83 (s, 3H), 3.25 (d, J=13.3 Hz,1H), 3.22-3.14 (m, 1H), 3.12-3.04 (m, 3H), 2.65 (td, J=12.9, 2.7 Hz,1H), 2.47-2.41 (m, 4H), 1.87-1.83 (m, 1H), 1.66 (qd, J=12.6, 4.1 Hz,1H), 1.61-1.53 (m, 5H), 1.45-1.41 (m, 2H). ¹³C NMR (151 MHz, CDCl₃) δ24.01, 24.04, 26.03, 31.72, 32.59, 35.61, 42.84, 46.71, 54.32, 54.42,55.26, 62.61, 109.95, 110.38, 120.66, 126.47, 126.49, 127.15, 133.53,156.74, 168.41. HRMS (ESI-TOF) calcd for C₁₉H₂₉N₂O₂ 317.2223 (M+H⁺),found 317.2226.

1-(4-(2-Methoxyphenyl)piperidin-1-yl)-2-morpholinoethan-1-one (53).4-(2-methoxyphenyl)piperidine (30 mg, 0.16 mmol), morpholin-4-ylaceticacid (27 mg, 0.19 mmol, 1.2 equiv.) and DIPEA (0.084 mL, 0.48 mmol, 3.0equiv.) in anhydrous DMF (1.0 mL) were added EDC (45 mg, 0.23 mmol, 1.5equiv.) and HOAt (32 mg, 0.23 mmol, 1.5 equiv.). The reaction mixturewas stirred at room temperature for 2 days. H₂O (1 mL) was added to thereaction mixture and product was extracted with EtOAc (2×1 mL). Thecombined organic layers were concentrated under reduced pressure. Theremaining residue was purified by PTLC (EtOAc/MeOH, 5/1) providing thetitle compound 53 as a colorless oil (35 mg, 70%). ¹H NMR (400 MHz,CDCl₃) δ 7.21 (td, J=7.8, 1.7 Hz, 1H), 7.11 (dd, J=7.6, 1.7 Hz, 1H),6.98-6.84 (m, 2H), 4.74 (d, J=12.9 Hz, 1H), 4.18 (d, J=13.4 Hz, 1H),3.83 (s, 3H), 3.74 (t, J=4.7 Hz, 4H), 3.28 (d, J=13.5 Hz, 1H), 3.24-3.07(m, 3H), 2.72-2.61 (m, 1H), 2.60-2.47 (m, 4H), 1.88 (t, J=14.4 Hz, 2H),1.69-1.59 (m, 2H). HRMS (ESI-TOF) calcd for C₁₈H₂₇N₂O₃ 319.2016 (M+H⁺),found 319.2017.

1-(2-(4-(2-Methoxyphenyl)piperidin-1-yl)-2-oxoethyl)pyridin-2(1H)-one(54). 4-(2-methoxyphenyl)piperidine (50 mg, 0.26 mmol),(2-oxo-2H-pyridin-1-yl)-acetic acid (48 mg, 0.31 mmol, 1.2 equiv.) andtriethylamine (0.054 mL, 0.39 mmol, 1.5 equiv.) in anhydrous DMF (1.0mL) were added EDC (76 mg, 0.39 mmol, 1.5 equiv.) and HOAt (53 mg, 0.39mmol, 1.5 equiv.). The reaction mixture was stirred at room temperaturefor ˜12 h before removing the solvent under reduced pressure. Theremaining residue was purified by PTLC (EtOAc/MeOH, 6/1) providing thetitle compound 54 as a colorless oil (39 mg, 46%). ¹H NMR (600 MHz,CDCl₃) δ 7.39-7.30 (m, 2H), 7.20 (ddd, J=8.2, 7.4, 1.7 Hz, 1H), 7.12(dd, J=7.5, 1.7 Hz, 1H), 6.93 (td, J=7.5, 1.1 Hz, 1H), 6.87 (dd, J=8.2,1.1 Hz, 1H), 6.58 (ddd, J=9.2, 1.4, 0.7 Hz, 1H), 6.21 (td, J=6.7, 1.4Hz, 1H), 4.86 (d, J=15.2 Hz, 1H), 4.80-4.69 (m, 2H), 4.15-4.04 (m, 1H),3.83 (s, 3H), 3.31-3.16 (m, 2H), 2.75 (td, J=13.0, 2.9 Hz, 1H),1.97-1.90 (m, 1H), 1.90-1.83 (m, 1H), 1.72-1.58 (m, 2H). ¹³C NMR (151MHz, CDCl₃) δ 30.90, 31.84, 34.98, 42.98, 45.82, 48.40, 54.87, 105.52,109.56, 109.96, 120.22, 120.29, 126.06, 126.91, 132.51, 138.06, 139.59,156.27, 161.96, 164.46. HRMS (ESI-TOF) calcd for C₁₉H₂₃N₂O₃ 327.1703(M+H⁺), found 327.1705.

1-(4-(2-Methoxyphenyl)piperidin-1-yl)-2-phenylethan-1-on (55). To amixture of 4-(2-methoxyphenyl)piperidine (30 mg, 0.16 mmol) andtriethylamine (0.073 mL, 0.24 mmol, 1.5 equiv.) in anhydrous CH₂Cl₂ (1.0mL) was added phenylacetyl chloride (26 mg, 0.17 mmol, 1.1 equiv.) underN₂ at 0° C. The reaction mixture was stirred at room temperature for 1 hbefore removing the solvent under reduced pressure. The remainingresidue was purified by PTLC (Hexanes/EtOAc, 2/1) providing the titlecompound 55 as a white solid (15 mg, 31%). ¹H NMR (500 MHz, CDCl₃) δ7.36-7.27 (m, 3H), 7.27-7.14 (m, 3H), 7.03 (dd, J=7.5, 1.7 Hz, 1H),6.94-6.82 (m, 2H), 4.81 (d, J=13.1 Hz, 1H), 3.97 (d, J=13.4 Hz, 1H),3.80 (s, 3H), 3.78 (s, 2H), 3.17-3.04 (m, 2H), 2.67 (td, J=12.9, 2.8 Hz,1H), 1.83 (d, J=13.5 Hz, 1H), 1.73 (d, J=13.3 Hz, 1H), 1.59 (td, J=12.7,4.3 Hz, 1H), 1.31 (qd, J=12.6, 4.1 Hz, 1H). HRMS (ESI-TOF) calcd forC₂₀H₂₄NO₂ 310.1801 (M+H⁺), found 310.1801.

4-(2-Methoxyphenyl)-N-phenylpiperidine-1-carboxamide (56). To a solutionof 4-(2-methoxyphenyl)piperidine (50 mg, 0.26 mmol) in anhydrous DMF(1.0 mL) was added sodium hydride (in 60% oil, 12.5 mg, 0.31 mmol, 1.2equiv.) under N₂ at 0° C. The mixture was stirred at 0° C. for 15 min.Phenylisocyanate (37 mg, 0.31 mmol, 1.2 equiv.) in anhydrous DMF (0.5mL) was added to the mixture. The reaction was then allowed to warm toroom temperature. After stirring at room temperature for 1 h, thereaction was quenched with saturated aqueous NH₄Cl and the product wasextracted with EtOAc (2×10 mL). The combined organic layers were thendried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Theremaining residue was purified by PTLC (Hexanes/EtOAc, 1/1) providingthe title compound 56 as an off-white powder (71 mg, 89%). ¹H NMR (600MHz, CDCl₃) δ 7.41-7.36 (m, 2H), 7.36-7.25 (m, 2H), 7.24-7.13 (m, 2H),7.03 (tt, J=7.4, 1.2 Hz, 1H), 6.94 (td, J=7.5, 1.1 Hz, 1H), 6.88 (dd,J=8.1, 1.1 Hz, 1H), 6.39 (brs, 1H), 4.24-4.18 (m, 2H), 3.84 (s, 3H),3.17 (tt, J=12.1, 3.5 Hz, 1H), 3.03 (td, J=13.0, 2.6 Hz, 2H), 1.92-1.86(m, 2H), 1.76-1.66 (m, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 31.26, 34.92,44.81, 54.85, 76.31, 76.81, 76.91, 76.99, 109.94, 119.33, 119.36,120.24, 120.25, 122.45, 122.49, 126.06, 126.79, 128.40, 128.43, 154.45,156.27. HRMS (ESI-TOF) calcd for C₁₉H₂₃N₂O₂ 311.1754 (M+H⁺), found311.1753.

2-Phenyl-1-(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)ethan-1-one(57). To a mixture of 4-(2-(trifluoromethyl)phenyl)piperidinehydrochloride (40 mg, 0.15 mmol) in anhydrous CH₂Cl₂ (1.5 mL) andpyridine (0.5 mL) was added phenylacetylchloride (26 mg, 0.17 mmol, 1.1equiv.) under N₂ at 0° C. The reaction mixture was stirred at roomtemperature for 12 h before removing the solvent under reduced pressure.The remaining residue was purified by PTLC (Hexanes/EtOAc, 2/1)providing the title compound 57 as a colorless oil (40 mg, 77%). ¹H NMR(600 MHz, CDCl₃) δ 7.61 (dd, J=7.9, 1.2 Hz, 1H), 7.51-7.45 (m, 1H),7.38-7.22 (m, 7H), 4.88-4.81 (m, 1H), 4.02-3.96 (m, 1H), 3.84-3.75 (m,2H), 3.15-3.04 (m, 2H), 2.65 (td, J=13.0, 2.8 Hz, 1H), 1.82 (d, J=13.3Hz, 1H), 1.69 (d, J=13.2 Hz, 1H), 1.63 (qd, J=12.6, 4.2 Hz, 1H), 1.31(qd, J=12.6, 4.1 Hz, 1H). ¹³C NMR (151 MHz, CDCl₃) δ 32.46, 33.25,37.85, 40.91, 42.24, 46.50, 125.05, 125.42, 125.46, 125.91, 126.40,127.37, 127.55, 128.21, 128.34, 131.65, 134.85, 143.64, 168.99. HRMS(ESI-TOF) calcd for C₂₀H₂₁F3NO 348.1570 (M+H⁺), found 348.1572.

1-(4-(3-Methoxyphenyl)piperidin-1-yl)-2-phenylethan-1-one (58). To amixture of 4-(2-(trifluoromethyl)phenyl)piperidine hydrochloride (40 mg,0.15 mmol) in anhydrous CH₂Cl₂ (1.5 mL) and pyridine (0.5 mL) was addedphenylacetylchloride (26 mg, 0.17 mmol, 1.1 equiv.) under N₂ at 0° C.The reaction mixture was stirred at room temperature for 12 h beforeremoving the solvent under reduced pressure. The remaining residue waspurified by PTLC (Hexanes/EtOAc, 2/1) providing the title compound 58 asa colorless oil (40 mg, 44%). ¹H NMR (500 MHz, CDCl₃) δ 7.37-7.28 (m,3H), 7.28-7.17 (m, 3H), 6.78-6.69 (m, 2H), 6.67-6.65 (m, 1H), 4.81 (d,J=13.3 Hz, 1H), 3.98 (d, J=13.7 Hz, 1H), 3.83-3.73 (m, 4H), 3.10-3.01(m, 1H), 2.70-2.59 (m, 2H), 1.87 (d, J=13.5 Hz, 1H), 1.74 (d, J=14.7 Hz,1H), 1.65-1.56 (m, 1H), 1.38-1.23 (m, 2H). HRMS (ESI-TOF) calcd forC₂₀H₂₄NO₂ 310.1801 (M+H⁺), found 310.1801.

General Procedure 5:

To a mixture of 1-phenylacetyl-piperazin hydrochloride (30 mg, 0.13mmol), phenylboronic acid (2.0 equiv.) and triethylamine (0.092 mL, 0.66mmol, 5.0 equiv.) in C1CH₂CH₂C1 (1.0 mL) was added Cu(OAc)₂ (48 mg, 0.17mmol, 2.0 equiv.). The reaction mixture was stirred at 50° C. for 12 hbefore removing the solvent under reduced pressure. The remainingresidue was purified by PTLC (Hexanes/EtOAc, 1/1) providing the titlecompound.

2-phenyl-1-(4-phenylpiperazin-1-yl)ethan-1-one (59). (10 mg, colorlessoil, 27%): ¹H NMR (500 MHz, CDCl₃) δ 7.36-7.30 (m, 3H), 7.30-7.21 (m,4H), 6.92-6.85 (m, 3H), 3.84-3.77 (m, 4H), 3.63-3.57 (m, 2H), 3.17-3.11(m, 2H), 2.99-2.95 (m, 2H). HRMS (ESI-TOF) calcd for C₁₈H₂₁N₂O 281.1648(M+H⁺), found 281.1649.

1-(4-(4-methoxyphenyl)piperazin-1-yl)-2-phenylethan-1-one (60). (7.2 mg,colorless oil, 18%): ¹H NMR (500 MHz, CDCl₃) δ 7.36-7.29 (m, 3H),7.29-7.25 (m, 4H), 6.88-6.79 (m, 2H), 3.83-3.74 (m, 7H), 3.62-3.56 (m,2H), 3.01 (t, J=5.2 Hz, 2H), 2.87-2.83 (m, 2H). HRMS (ESI-TOF) calcd forC₁₉H₂₃N₂O₂ 311.1754 (M+H⁺), found 311.1755.

1-(4-(4-methoxyphenyl)piperazin-1-yl)-2-phenylethan-1-one (61). (1.6 mg,white solid, 3.0%): ¹H NMR (500 MHz, CDCl₃) δ 7.38-7.24 (m, 6H),7.21-7.17 (m, 2H), 3.86-3.78 (m, 4H), 3.63 (t, J=5.2 Hz, 2H), 3.26 (t,J=5.3 Hz, 2H), 3.08 (t, J=5.1 Hz, 2H). HRMS (ESI-TOF) calcd forC₂₀H₁₉F₆N₂O 417.1396 (M+H⁺), found 417.1397

1-(4-(2-phenoxyphenyl)piperazin-1-yl)-2-phenylethan-1-one (62). (3.3 mg,colorless oil, 6.8%): ¹H NMR (500 MHz, CDCl₃) δ 7.34-7.20 (m, 6H),7.13-6.85 (m, 8H), 3.72 (s, 2H), 3.60 (t, J=5.1 Hz, 2H), 3.40-3.34 (m,2H) 3.02 (t, J=5.1 Hz, 2H), 2.87 (t, J=5.0 Hz, 2H). HRMS (ESI) calcd forC₂₄H₂₅N₂O₂ 373.191 (M+H⁺), found 373.1909.

Tables 1-3 illustrate proteins and binding sites described herein.

TABLE 1 Accession Labeled # Protein Name Peptide Peptide Sequence ProbesFamily Q9NUJ1 ABHD10 285-300 ADIQLLVYTIDDLIDK (SEQ ID 3 EnzymesAbhydrolase NO: 97) domain- containing protein 10, mitochondrial Q9NUJ1ABHD10 209-223 YSEEGVYNVQYSFIK (SEQ ID NO: 13 14 Enzymes Abhydrolase 98)15 3 4 domain- 8 containing protein 10, mitochondrial Q99798ACO2 Aconitate 32-50 VAMSHFETNEYIHYDLLEK (SEQ 6 Enzymes hydratase,ID NO: 99) mitochondrial P24666 ACP1 Low 42-59 VDSAATSGYEIGNPPDYR 13Enzymes molecular (SEQ ID NO: 1) weight phosphotyrosine proteinphosphatase P68133 ACTA1 Actin, 241-256 SYELPDGQVITIGNER (SEQ ID 13 3 9Adapter, alpha skeletal NO: 100) Scaffolding, muscle Modulator ProteinsP68133 ACTA1 Actin, 71-86 YPIEHGIITNWDDMEK (SEQ ID 13 Adapter,alpha skeletal NO: 101) Scaffolding, muscle Modulator Proteins P62736ACTA2 Actin, 241-256 SYELPDGQVITIGNER (SEQ ID 13 9 Adapter,aortic smooth NO: 102) Scaffolding, muscle Modulator Proteins P62736ACTA2 Actin, 71-86 YPIEHGIITNWDDMEK 13 Adapter, aortic smooth NO: 103)Scaffolding, muscle Modulator Proteins P60709 ACTB Actin, 148-177TTGIVMDSGDGVTHTVPIYEGYA 14 13 Adapter, cytoplasmic 1LPHAILR (SEQ ID NO: 104) Scaffolding, Modulator Proteins P60709ACTB Actin, 197-206 GYSFTTTAER (SEQ ID NO: 105) 3 Adapter, cytoplasmic 1Scaffolding, Modulator Proteins P60709 ACTB Actin,LCYVALDFEQEMATAASSSSLEK 13 14 Adapter, cytoplasmic 1 216-238(SEQ ID NO: 106) 3 9 8 Scaffolding, Modulator Proteins P60709ACTB Actin, 239-254 SYELPDGQVITIGNER (SEQ ID 13 14 Adapter,cytoplasmic 1 NO: 107) 3 9 8 Scaffolding, Modulator Proteins P60709ACTB Actin, 96-113 VAPEEHPVLLTEAPLNPK(SEQ ID 14 3 Adapter, cytoplasmic 1NO: 108) 13 Scaffolding, Modulator Proteins Q562R1 ACTBL2 Beta- 240-255SYELPDGQVITIGNER (SEQ ID 13 Adapter, actin-like NO: 109) Scaffolding,protein 2 Modulator Proteins Q562R1 ACTBL2 Beta- 97-114VAPDEHPILLTEAPLNPK (SEQ ID 13 Adapter, actin-like NO: 110) Scaffolding,protein 2 Modulator Proteins O96019 ACTL6A Actin- 25-34AGYAGEDCPK (SEQ ID NO: 111) 3 Transcription like protein 6A factors,Regulators P12814 ACTN1 Alpha- 237-254 AIMTYVSSFYHAFSGAQK (SEQ ID 13Adapter, actinin-1 NO: 112) Scaffolding, Modulator Proteins P12814ACTN1 Alpha- 377-387 GYEEWLLNEIR (SEQ ID NO: 113) 13 Adapter, actinin-1Scaffolding, Modulator Proteins O43707 ACTN4 Alpha- 256-273AIMTYVSSFYHAFSGAQK (SEQ ID 13 Channels, actinin-4 NO: 114) Transporters,Receptors O43707 ACTN4 Alpha- 396-406 GYEEWLLNEIR (SEQ ID NO: 115) 13Channels, actinin-4 Transporters, Receptors O43707 ACTN4 Alpha- 470-494VEQIAAIAQELNELDYYDSHNVN 14 Channels, actinin-4 TR (SEQ ID NO: 116)Transporters, Receptors O43707 ACTN4 Alpha- 792-805ACLISLGYDVENDR (SEQ ID: 14 Channels, actinin-4 117) Transporters,Receptors Q8NI60 ADCK3 277-295 LGQMLSIQDDAFINPHLAK 14 Enzymes Chaperone(SEQ ID NO: 2) activity of bc1 complex-like, 14 mitochondrial P55263ADK Adenosine 209-224 IFTLNLSAPFISQFYK 2 Enzymes kinase (SEQ ID NO: 3)P30520 ADSS 431-441 FIEDELQIPVK 14 Enzymes Adenylosuccinate(SEQ ID NO: 4) synthetase isozyme 2 Q53H12 AGK 283-304LASYWAQPQDALSQEVSPEVWK 14 Enzymes Acylglycerol (SEQ ID NO: 118) kinase,mitochondrial AGPS O00116 Alkyldihydroxya 587-603GISDPLTVFEQTEAAAR (SEQ ID 13 14 Enzymes cetonephosphate NO: 119)synthase, peroxisomal O43865 AHCYL1 250-261 GIVEESVTGVHR  6Transcription Putative (SEQ ID NO: 120) factors, adenosylhomocyRegulators steinase 2 Q96HN2 AHCYL2 Putative 331-342 GIVEESVTGVHR  6Enzymes adenosylhomocy (SEQ ID NO: 121) steinase 3 O95433 AHSA1 225-246VFTTQELVQAFTHAPATLEADR 4 Chaperones Activator of 90 (SEQ ID NO: 122)kDa heat shock protein ATPase homolog 1 O95433 AHSA1 322-328YYFEGIK (SEQ ID NO: 123) 4 Chaperones Activator of 90 kDa heat shockprotein ATPase homolog 1 O95831 AIFM1 PYWHQSMIEWSDLGPDVGYEAIG 3 2 4Enzymes Apoptosis- 475-510 LVDSSLPTVGVFAK 6 inducing factor(SEQ ID NO: 5) 1, mitochondrial P54886 ALDH18A1 650-662FASYLTFSPSEVK (SEQ ID NO: 14 Enzymes Delta-1- (12) pyrroline-5-carboxylate synthase Q3SY69 ALDHIL2 152-172 AGFSVFWADDGLDTGPILLQR 6Enzymes Mitochondrial (SEQ ID NO: 125) 10- formyltetraydro folatedehydrogen P49419 ALDH7A1 139-162 ILVEGVGEVQEYVDICDYAVGLSR 13 8 EnzymesAlpha- (SEQ ID NO: 6) aminoadipic semialdehyde dehydrogenase Q9UJX3ANAPC7 407-424 LDCYEGLIECYLASNSIR (SEQ ID 3 Uncategorized Anaphase-NO: 126) promoting complex subunit 7 ANP32A Acidic 117-132SLDLFNCEVTNLNDYR (SEQ ID 13 Transcription Q10567 leucine-rich NO: 127)factors, nuclear Regulators phosphoprotein 32 family member A Q92688ANP32B Acidic 117-132 SLDLFNCEVTNLNDYR (SEQ ID 13 Chaperonesleucine-rich NO: 128) nuclear phosphoprotein 32 family member B Q10567AP1B1 AP-1 902-913 LTNGIWVLAELR (SEQ ID NO: 13 Channels, complex subunit129) Transporters, beta-1 Receptors Q9BZZ5 API5 Apoptosis 182-196VLEDVTFEEFVLFMK (SEQ ID 4 Uncategorized inhibitor 5 NO: 130) Q9BZZ5API5 Apoptosis 131-148 GTLGGLFSQILQGEDIVR (SEQ ID 4 Uncategorizedinhibitor 5 NO: 131) Q9BZZ5 API5 Apoptosis 211-237QQLVELVAEQADLEQTFNPSDPD 4 Uncategorized inhibitor 5CVDR (SEQ ID NO: 132) Q9BUR5 APOO 173-182 GYIVIEDLWK (SEQ ID NO: 133)14 4 2 Channels, Apolipoprotein Transporters, O Receptors P84077ARF1 ADP- 39-59 LGEIVTTIPTIGFNVETVEYK 13 3 2 Channels, ribosylation(SEQ ID NO: 7) 8 Transporters, factor 1 Receptors P61204 ARF3 ADP- 39-59LGEIVTTIPTIGFNVETVEYK 13 3 2 Channels, ribosylation (SEQ ID NO: 7) 8Transporters, factor 3 Receptors P18085 ARF4 ADP- 39-59LGEIVTTIPTIGFNVETVEYK 13 3 2 Channels, ribosylation (SEQ ID NO: 7) 8Transporters, factor 4 Receptors P84085 ARF5 ADP- 39-59LGEIVTTIPTIGFNVETVEYK 13 3 2 Channels, ribosylation (SEQ ID NO: 7) 8Transporters, factor 5 Receptors P40616 ARL1 ADP- 163-178GTGLDEAMEQLVETLK  14 13 Transcription ribosylation (SEQ ID NO: 9)factors factor-like Regulators protein 1 P40616 ARL1 ADP- 37-59LQVGEVVTTIPTIGFNVETVTY 13 Transcription ribosylation (SEQ ID NO: 10)factors factor-like Regulators protein 1 O43681 ASNA1 ATPase 131-153MMQEAMSAFPGIDEAMSYAEVM 14 Enzymes ASNA1 R (SEQ ID NO: 134) Q9NV17 ATAD3A287-294 AFVTDWDK (SEQ ID NO: 135) 4 6 Enzymes ATPase family AAA domain-containing protein 3A P31939 ATIC 178-194 AFTHTAQYDEAISDYFR 13  EnzymesBifunctional (SEQ ID NO: 11) purine biosynthesis protein PURH P05023ATP1A1 360-377 NLEAVETLGSTSTICSDK (SEQ ID 13 14 Channels,Sodium/potassium- NO: 136) Transporters, transporting ReceptorsATPase subunit apha P05023 ATP1A1 894-911 WINDVEDSYGQQWTYEQR (SEQ 9Channels, Sodium/potassium- ID NO: 137) Transporters, transportingReceptors ATPase subunit apha P16615 ATP2A2 335-352SLPSVETLGCTSVICSD (SEQ ID 14 Channels, Sarcoplasic/ NO: 138)Transporters, endoplasmic Receptors reticulum calcium ATPase P20020ATP2B1 Plasma 824-840 EASDIILTDDNFTSIVK (SEQ ID 14 Channels, membraneNO: 139) Transporters, calcium- Receptors transporting ATPase 1 P23634ATP2B4 Plasma 812-828 EASDILTDDFTSIV (SEQ ID 14 Channels, membraneNO: 140) Transporters, calcium- Receptors transporting ATPase 4 P25705ATP5A1 ATP 104-123 GMSLNLEPDNVGVVVFGNDK 14 3  Channels, synthase subunit(SEQ ID NO: 141) 13 Transporters, alpha, Receptors mitochondrial P25705ATP5A1 ATP 442-463 EVAAFAQFGSDLDAATQQLLSR 13 14 Channels,synthase subunit (SEQ ID NO: 142) 3 2 9 Transporters, alpha, 8 Receptorsmitochondrial P06576 ATP5B ATP 144-155 IMNVGEPIDER (SEQ ID NO: 143) 2 6Channels, synthase subunit Transporters, beta, Receptors mitochondrialP06576 ATP5B ATP 226-239 AHGGYSVFAGCGER (SEQ ID NO: 6 Channels,synthase subunit 144) Transporters, beta, Receptors mitochondrial P06576ATP5B ATP 242-259 EGNDLYHEMIESGVINLK (SEQ  9 6 Channels,synthase subunit NO: 145) Transporters, beta, Receptors mitochondrialP06576 ATP5B ATP 295-310 DQEGQDVLLFIDNIFR (SEQ ID 6 Channels,synthase subunit NO: 146) Transporters, beta, Receptors mitochondrialP06576 ATP5B ATP 352-387 GSITSVQAIYVPADDLTDPAPATT 14 9 6 Channels,synthase subunit FAHLDATTVLSR (SEQ ID NO: Transporters, beta, 147)Receptors mitochondrial P06576 ATP5B ATP 388-406AIAELGIYPAVDPLDSTSR (SEQ ID 13 14 Channels, synthase subunit NO: 148)3 2 6 Transporters, beta, 8 Receptors mitochondrial P06576 ATP5B ATP407-422 IMDPNIVGSEHYDVAR (SEQ ID 14   Channels, synthase subunitNO: 149) Transporters, beta, Receptors mitochondrial P06576 ATP5B ATP433-451 SLQDIIAILGMDELSEEDK (SEQ ID 14 6 Channels, synthase subunitNO: 150) Transporters, beta, Receptors mitochondrial P06576 ATP5B ATP463-480 FLSQPFQVAEVFTGHMGK (SEQ 6 Channels, synthase subunit ID NO: 151)Transporters, beta, Receptors mitochondrial P06576 ATP5B ATP 95-109LVLEVAQHLGESTVR (SEQ ID 13 6 Channels, synthase subunit NO: 152Transporters, beta, Receptors mitochondrial P36542 ATP5C1 ATP 116-126SEVATLTAAGK (SEQ ID NO: 153) 6 Channels, synthase subunit Transporters,gamma, Receptors mitochondrial P24539 ATP5F1 ATP 116-126YGPFVADFADK (SEQ ID NO: 154) 14 Channels, synthase subunit Transporters,b, mitochondrial Receptors P24539 ATP5F1 ATP 56-70YGLIPEEFFQFLYPK (SEQ ID NO: 14 4 2 Channels, synthase subunit 155) 13Transporters, b, mitochondrial Receptors P24539 ATP5F1 ATP 71-90TGVTGPYVLGTGLILYALSK (SEQ 13 Channels, synthase subunit ID NO: 156)Transporters, b, mitochondrial Receptors ATP5F1 ATP P21281 ATP6V1B2 V-437-457 AVVGEEALTSDDLLYLEFLQK 14 Channels, type proton (SEQ ID NO: 157)Transporters, ATPase subunit Receptors B, brain isoform P21281ATP6V1B2 V- 83-93 SGQVLEVSGSK (SEQ ID NO: 158) 13 Channels, type protonTransporters, ATPase subunit Receptors B, brain isoform P36543ATP6V1BE1 V- 200-212 LDLIAQQMMPEVR (SEQ ID NO: 13 Channels, type proton159) Transporters, ATPase subunit Receptors E 1 P46379 BAG6 Large332-344 LLGNTFVALSDLR (SEQ ID NO: 8 Chaperones proline-rich 160)protein BAG6 Q07812 BAX Apoptosis 66-78 IGDELDSNMELQR (SEQ ID NO: 13Uncategorized regulator BAX 161) O75934 BCAS2 Pre- 137-151VYNENLVHMIEHAQK (SEQ ID 4 Uncategorized mRNA-splicing NO: 162)factor SPF27 Q13867 BLMH  203-218 GEISATQDVMMEEIFR 13 Enzymes Bleomycin(SEQ ID NO: 13) hydrolase Q13867 BLMH  111-124 CYFFLSAFVDTAQR 14 EnzymesBleomycin (SEQ ID NO: 12) hydrolase P35613 BSG Basigin 283-300SELHIENLNMEADPGQYR (SEQ ID 13 14 Uncategorized NO: 163) 4 P35613BSG Basigin 228-243 SSEHINEGETAMLVCK (SEQ ID 2 Uncategorized NO: 164)Q4ZIN3 C19orf6 254-271 LLLDEFLGYDDILMSSVK (SEQ ID  9 UncategorizedMembralin NO: 165) Q07021 C1QBP 247-276 GVDNTFADELVELSTALEHQEYIT 13 14Transcription Complement FLEDLK (SEQ ID N: 166) 3 9 factors,component 1 Q Regulators subcomponent- binding protein Q07021 C1QBP155-174 VEEQEPELTSTPNFVVEVIK(SEQ 13 14 Transcription ComplementID NO: 167) 3 9 factors, component 1 Q Regulators subcomponent-binding protein Q07021 C1QBP 105-119 MSGGWELELNGTEAK (SEQ ID 9Transcription Complement NO: 168) factors, component 1 Q Regulatorssubcomponent- binding protein Q07021 C1QBP 181-207ALVLDCHYPEDEVGQEDEAESDIF 13 9 Transcription ComplementSIR (SEQ ID NO: 169) factors, component 1 Q Regulators subcomponent-binding protein Q07021 C1QBP 81-91 AFVDFLSDEIK (SEQ ID NO: 170) 9Transcription Complement factors, component 1 Q Regulators subcomponent-binding protein Q07021 C1QBP 129-154 ITVTFNINNSIPPTFDGEEEPSQGQ 9Transcription Complement K (SEQ ID NO: 171) factors, component 1 QRegulators subcomponent- binding protein Q07021 C1QBP 208-220EVSFQSTGESEWK (SEQ ID NO: 3 9 Transcription Complement 172) factors,component 1 Q Regulators subcomponent- binding protein P62158 CALM3128-149 EADIDGDGQVNYEEFVQMMTAK 13 Adapter, Calmodulin (SEQ ID NO: 173)Scaffolding, Modulator Proteins P62158 CALM3 39-75SLGQNPTEAELQDMINEVDADGN 14 Adapter, CalmodulinGTIDFPEFLTMMAR (SEQ ID NO: Scaffolding, 174) Modulator Proteins P27797CALR 323-351 SGTIFDNFLITNDEAYAEEFGNET 13 9 Chaperones Calreticulin WGVTK6 (SEQ ID NO: 14) P27797 CALR 99-111 HEQNIDCGGGYVK 6 ChaperonesCalreticulin (SEQ ID NO: 15) P27824 CANX Calnexin 235-274THLYTLILNPDNSFEILVDQSVVN 6 Chaperones SGNLLNDMTPPVNPSR (SEQ ID NO: 175)P07384 CAPN1 175-193 LVFVHSAEGNEFWSALLEK 14 Enzymes Calpain-1(SEQ ID NO: 16) catalytic subunit Q96A33 CCDCC47 197-212LNQENEHIYNLWCSGR (SEQ ID 4 2 Uncategorized Coiled-coil NO: 177) domain-containing protein 47 Q96A33 CCDCC47 375-392 DMEALLPLMNMVIYSIDK (SEQ 6Uncategorized Coiled-coil ID NO: 178) domain- containing protein 47Q96ER9 CCDCC51 86-96 YEEFVGLNEVR (SEQ ID NO: 179) 14 UncategorizedCoiled-coil domain- containing protein 51 P78371 CCT2 T- 294-322QLIYNYPEQLFGAAGVMAIEHAD 14 Chaperones complex proteinFAGVER (SEQ ID NO: 180) 1 subunit beta P78371 CCT2 T- 502-516QVLLSAAEAAEVILR (SEQ ID NO:  14 3 Chaperones complex protein 181)1 subunit beta P78371 CCT2 T- 90-111 VQDDEVGDGTTSVTVLAAELLR 14Chaperones complex protein (SEQ ID NO: 182) 1 subunit beta P49368CCT3 T- 439-449 AVAQALEVIPR (SEQ ID NO: 183) 14 Chaperonescomplex protein 1 subunit gamma P49368 CCT3 T- 86-127TQDEEVGDGTTSVIILAGEMLSVA 14 Chaperones complex proteinEHFLEQQMHPTVVISAYR (SEQ ID 1 subunit NO: 184) gamma P50991 CCT4 T-175-193 VVSQYSSLLSPMSVNAVMK (SEQ 2 Chaperones complex proteinID NO: 185) 1 subunit delta P50991 CCT4 T- 453-481AFADAMEVIPSTLAENAGLNPIST 14 4 2 Chaperones complex proteinVTELR (SEQ ID NO: 186) 1 subunit delta P48643 CCT5 T- 294-323ETGANLAICQWGFDDEANHLLLQ 6 Chaperones complex proteinNLPAVR (SEQ ID NO: 187) 1 subunit epsilon P48643 CCT5 T- 324-340WVGGPEIELIAIATGGR (SEQ ID 14 3 Chaperones complex protein NO: 188) 13 61 subunit epsilon P48643 CCT5 T- 450-478 AFADALEVIPMALSENSGMNPIQT 14 6Chaperones complex protein MTEVR (SEQ ID NO: 189) 1 subunit epsilonP48643 CCT5 T- 97-126 SQDDEIGDGTTGVVVLAGALLE 13 14 Chaperonescomplex protein AEQLLDR (SEQID NO: 190) 6 9 1 subunit epsilon P40227CCT6A T- 400-424 NAIDDGCVVPGAGAVEVAMAEA 9 Chaperones complex proteinLIK (SEQ ID NO: 191) 1 subunit zeta Q99832 CCT7 T- 85-106SQDAEVGDGTTSVTLLAAEFLK 13 Chaperones complex protein (SEQ ID NO: 192)1 subunit eta P50990 CCT8 T- 441-450 FAEAFEAIPR (SEQ ID NO: 193) 8Chaperones complex protein 1 subunit theta Q16543 CDC37 Hsp90 287-307LGPGGLDPVEVYESLPEELQK 8 Chaperones co-chaperone (SEQ ID NO: 194) Cdc37Q96JB5 CDK5RAP3 351-367 NQFLDELMELEIFLAQR (SEQ ID 3 Adapter, CDK5NO: 195) Scaffolding, regulatory Modulator subuni- Proteins associatedprotein 3 Q07065 CKAP4 312-326 STLQTMESDIYTEVR (SEQ ID NO: 13 14Adapter, Cytoskeleton- 196) 9 8 Scaffolding, associated  Modulatorprotein 4 Proteins P12277 CKB Creatine 224-236 TFLVWVNEEDHLR 3 Enzymeskinase B-type (SEQ ID NO: 19) P12277 CKB Creatine 342-358LGFSEVELVQMVVDGVK 3 13 Enzymes kinase B-type (SEQ ID NO: 21) P12277CKB Creatine 367-381 LEQGQAIDDLMPAQK 13 Enzymes kinase B-type(SEQ ID NO: 22) P12277 CKB Creatine 14-32 FPAEDEFPDLSAHNNHMAK 3 Enzymeskinase B-type (SEQ ID NO: 17) P12277 CKB Creatine 157-172LAVEALSSLDGDLAGR 13 Enzymes kinase B-type (SEQ ID NO: 18) P12277CKB Creatine 253-265 FCTGLTQIETLFK 13 Enzymes kinase B-type(SEQ ID NO: 20) P12532 CKMT1B 257-269 SFLIWVNEEDHTR 3 EnzymesCreatine kinase (SEQ ID NO: 23) U-type, motochondrial O75503CLN5 Ceroid- 74-96 YTFCPTGSPIPVMEGDDDIEVFR 9 Uncategorizedlipofuscinosis (SEQ ID NO: 197) neuronal protein 5 Q9H078 CLPB 630-650VVNQLAAAYEQDLLPGGCTLR 14 Enzymes Caseinolytic (SEQ ID NO: 198)peptidase B protein homolog Q16740 CLPP Putative 215-226 QSLQVIESAMER 6Enzymes ATP-dependent (SEQ ID NO: 24) Clp protease proteolytic subunitO96005 CLPTM1 Cleft 325-346 SPWNFLGDELYEQSDEEQDSVK 13 14 Uncategorizedlip and palate (SEQ ID NO: 199) 2 6 transmembrane protein 1 O96005CLPTM1 Cleft 548-562 ALNTFIDDLFAFVIK (SEQ ID NO: 2 Uncategorizedlip and palate 200) transmembrane protein 1 P53618 COPB1 262-279YEAAGTLVTLSSAPTAIK (SEQ ID 13 Channels, Coatomer NO: 201) Transporters,subunit beta Receptors Q9BT78 COPS4 COP9 154-170LYLEDDDPVQAEAYINR (SEQ ID 13 15 Uncategorized signalosome NO: 202)complex subunit 4 Q5HYK3 COQ5 2- 258-279 LYDLYSFQVIPVLGEVIAGDWK 14 2Enzymes methoxy-6- (SEQ ID NO: 203) polyprenyl-1,4- benzoquinolmethylase, Q7KZN9 COX15 296-313 MGESWIPEDLFTFSPILR (SEQ ID 14Uncategorized Cytochrome NO: 204) coxidase assembly protein COX15 homoloP20674 COX5A 73-87 GINTLVTYDMVPEPK (SEQ ID NO: 13 14 Adapter, Cytochrome205) 3 2 9 Scaffolding, coxidase subunit Modulator 5A, Proteinsmitochondrial P23786 CPT2 Carnitine 363-382 DGSTAVHFEHSWGDGVAVLR 15 13Enzymes O- (SEQ ID NO: 206) palmitoyltransfe rase 2, mitochondrialP23786 CPT2 Carnitine 478-495 QYGQTVATYESCSTAAFK (SEQ 4 Enzymes O-ID NO: 207) palmitoyltransfe rase 2, mitochondrial Q9H3G5 CPVL Probable281-292 QNWFEAFEILDK (SEQ ID NO:  4 9 Enzymes serine 208)carboxypeptidase CPVL Q9H3G5 CPVL Probable 320-331CTEPEDQLYYVK (SEQ ID NO: 13 9 Enzymes serine 209) carboxypeptidase CPVLQ9H3G5 CPVL Probable 195-208 NNDFYVTGESYAGK (SEQ ID NO: 9 Enzymes serine210) carboxypeptidase CPVL P55060 CSEIL 32-52 FLESVEGNQNYPLLLLTLLEK 14 3Channels, Exportin-2 (SEQ ID NO: 211) Transporters, Receptors P55060CSEIL 396-418 FFEGPVTGIFSGYVNSMLQEYAK 14 Channels, Exportin-2(SEQ ID NO: 212) Transporters, Receptors P48729 CSNK1A1 84-106DYNVLVMDLLGPSLEDLFNFCSR 14 Enzymes Casein kinase I (SEQ ID NO: 25)isoform alpha 14 Uncategorized P67870 CSNK2B Casein 112-134VYCENQPMLPIGLSDIPGEAMVK kinase II subunit (SEQ ID NO: 26) beta Q12996CSTF3 440-464 YGDIPEYVLAYIDYLSHLNEDNNT 13 Uncategorized CleavageR (SEQ ID NO: 213) stimulation factor subunit 3 Q12996 CSTF3 319-330LFSDEAANIYER  13 14 Uncategorized Cleavage (SEQ ID NO: 214) stimulationfactor subunit 3 P35222 CTNNB1 648-661 NEGVATYAAAVLFR (SEQ ID NO:  14 13Adapter Catenin beta-1 215) Scaffolding, Modulator Proteins P07858 CTSB315-331 GQDHCGIESEVVAGIPR 13 4 2 Enzymes Cathepsin B (SEQ ID NO: 27) 9P07339 CTSD Cathespin 236-253 DPDAQPGGELMLGGTDSK 9 Enzymes D(SEQ ID NO: 28) P07339 CTSD Cathespin 288-309 EGCEAIVDTGTSLMVGPVDEVR13 14 Enzymes D (SEQ ID NO: 29) 15 4 6 9 8 P07339 CTSD Cathespin 314-331AIGAVPLIQGEYMIPCEK 14 15 Enzymes D (SEQ ID NO 30) 3 2 4 13 6 9 8 O43169CYB5B 138-144 YYTSESK (SEQ ID NO: 216) 4 2 Adapter Cytochrome b5Scaffolding, type B Modulator Proteins P00387 CYB5R3 235-241 LWYTLDR 3Enzymes NADH- (SEQ ID NO: 31) cytochrome b5 reductase 3 Q6UW02 CYP20A1397-413 TFSSLGFSGTQCPELR (SEQ ID 14 4 3 Enzymes Cytochrome NO: 217)P450 20A1 P61962 DCAF7 DDB1- 82-96 GVYPDLLATSGDYLR (SEQ ID 14Uncategorized and CUL4- NO: 218) associated factor 7 Q13561 DCTN2380-395 ENLATVEGNFASIDER (SEQ ID  13 6 Adapter Dynactin NO: 219)Scaffolding, subunit 2 Modulator Proteins Q9H773 DCTPP1 dCTP 90-109AALQEELSDVLIYLVALAAR (SEQ 14 4 Enzymes pyrophosphatase ID NO: 220) 1Q92841 DDX17 406-417 LIQLMEEIMAEK  13 14 Transcription Propable ATP-(SEQ ID NO: 221) 2 9 factors, dependent RNA Regulators helicase DDX17Q92841 DDX17 536-547 VLEEANQAINPK  3 Transcription Propable ATP-(SEQ ID NO: 222) factors, dependent RNA Regulators helicase DDX17 Q16698DECR1 2, 4- 299-315 FDGGEEVLISGEFNDLR 6 Enzymes dienoyl-CoA(SEQ ID NO: 32) reductase, mitochondrial Q15392 DHCR24 334-352SIFWELQDIIPFGNNPIFR (SEQ ID 3 15 2 Enzymes Delta(24)-sterol NO: 223)reductase Q15392 DHCR24 428-444 GNEAELYIDIGAYGEPR (SEQ ID 13 14 EnzymesDelta(24)-sterol NO: 224) 8 reductase Q9H2U1 DHX36 754-770SDHLTVVNAFEGWEEAR (SEQ ID 6 Transcription Probable ATP- NO: 225)factors, dependent RNA Regulators helicase A Q08211 DHX9 ATP- 448-456ISAVSVAER 3 Transcription dependent RNA (SEQ ID NO: 33) factors,helicase A Regulators Q08211 DHX9 ATP- 121-141 AENNSEVGASGYGVPGPTWDR 8Transcription dependent RNA (SEQ ID NO: 226) factors, helicase ARegulators Q9NR28 DIABLO Diablo  124-140 MNSEEEDEVWQVIIGAR (SEQ ID 13Uncategorized homolog, NO: 227) mitochondrial P09622 DLD 450-482VLGAHILGPGAGEMVEAALALE 14 4 Enzymes Dihydrolipoyl YGASCEDIAR 13dehydrogenase, (SEQ ID NO: 34) mitochondrial Q9NVH1 DNAJC11 DnaJ 207-226GWGELEFGAGDLQGPLFGLK 14 6 Chaperones homolog (SEQ ID NO: 228)subfamily C member 11 O00115 DNASE2 173-202 QLTYTYPWVYNYQLEGIFAQEFP 9Enzymes Deoxyribonucle DLENVVK (SEQ ID NO: 229) ase-2-alpha P42892 ECE1434-453 FCVSDTENNLGFALGPMFVK 14 13 Enzymes Endothelin- (SEQ ID NO: 230)converting enzyme 1 Q13011 ECH1 197-211 EVDVGLAADVGTLQR 13 14 EnzymesDelta(3,5)- (SEQ ID NO: 37) 15 3 4 Delta(2,4)- 6 8 dienoyl-CoAisomerase, mitochondrial Q13011 ECH1 149-158 YQETFNVIER 6 EnzymesDelta(3,5)- (SEQ ID NO: 36) Delta(2,4)- dienoyl-CoA isomerase,mitochondrial Q13011 ECH1 113-131 MFTAGIDLMDMASDILQPK 6 EnzymesDelta(3,5)- (SEQ ID NO: 35) Delta(2,4)- dienoyl-CoA isomerase,mitochondrial Q9NTX5 ECHDC1 272-283 ELYLEEALQNER (SEQ ID NO: 9 EnzymesEthylmalonyl- 231) CoA decarboxylase P68104 EEF1A1 135-146EHALLAYTLGVK (SEQ ID NO: 13 Transcription Elongation 232) factors,factor 1-alpha 1 Regulators P26641 EEF1G 379-400 GQELAFPLSPDWQVDYESYTWR13 Uncategorized Elongation (SEQ ID NO: 233) factor 1-gamma P26641 EEF1G58-85 VPAFEGDDGFCVFESNAIAYYVS 3 Uncategorized ElongationNEELR (SEQ ID NO: 234) factor 1-gamma P13639 EEF2 457-481YVEPIEDVPCGNIVGLVGVDQFLV 3 Transcription Elongation K (SEQ ID NO: 235)factors, factor 2 Regulators P13639 EEF2 740-765LMEPIYLVEIQCPEQVVGGIYGVL 3 Transcription Elongation NR (SEQ ID NO: 236)factors, factor 2 Regulators P13639 EEF2 768-785 HVFEESQVAGTPMFVVK (SEQ3 Transcription Elongation ID NO: 237) factors, factor 2 RegulatorsP60228 EIF3E 173-191 LASEILMQNWDAAMEDLTR (SEQ 2 Uncategorized EukaryoticID NO: 238) translation initiation factor 3 submit O00303 EIF3F 193-210EAPNPIHLTVDTSLQNGR (SEQ ID 3 6 Enzymes Eukaryotic NO: 239) translationinitiation factor 3 submit O00303 EIF3F 279-297 IQDALSTVLQYAEDVLSGK (SEQ3 9 Enzymes Eukaryotic ID NO: 240) translation initiation factor3 submit O15372 EIF3H 207-220 NSHLINVLMWELEK (SEQ ID NO: 2 UncategorizedEukaryotic 241) translation initiation factor 3 submit Q9Y262 EIF3L404-419 GDPQVYEELFSYSCPK (SEQ ID 13 Uncategorized Eukaryotic NO: 242)translation initiation factor 3 submit Q9Y262 EIF3L 243-262QLEVYTSGGDPESVAGEYGR 13 14 Uncategorized Eukaryotic (SEQ ID NO: 243)translation initiation factor 3 submit P60842 EIF4A1 69-82GYDVIAQAQSGTGK 14 13 Transcription Eukaryotic (SEQ ID NO: 39) 9 factors,initiation factor Regulators 4A-I Transcription P60842 EIF4A1 178-190MFVLDEADEMLSR 13 factors, Eukaryotic (SEQ ID NO: 38) Regulatorsinitiation factor Transcription 4A-I factors, Q14240 EIF4A2 70-83GYDVIAQAQSGTGK 13 Regulators Eukaryotic (SEQ ID NO: 40) Transcriptioninitiation factor factors, 4A-II Regulators Q15056 EIF4H 97-109EALTYDGALLGDR (SEQ ID NO: 9 Transcription Eukaryotic 244) factors,translation Regulators initiation factor Transcription 4H P55010EIF5 Eukaryotic 274-288 AMGPLVLTEVLFNEK (SEQ ID 14 3 2 Transcriptiontranslation NO: 245) 4 13 6 factors, initiation factor Regulators 5Q15717 ELAVL1 20-37 TNLIVNYLPQNMTQDELR (SEQ 13 4 2 TranscriptionELAV-like ID NO: 246) factors, protein 1 Regulators Q9NXB9 ELOVL2 42543AFDDEINAFLDNMFGPR (SEQ ID 14 9 Enzymes Elongation of  NO: 247)very long chain  fatty acids protein P50402 EMD Emerin 212-221APGAGLGQDR (SEQ ID NO: 248) 4 Adapter, Scaffolding, Modulator ProteinsP50402 EMD Emerin 89-103 GYNDDYYEESYFTTR (SEQ ID 6 8 Adapter, NO: 249)Scaffolding, Modulator Proteins P07099 EPHX1 Epoxide 329-338FSTWTNTEFR (SEQ ID NO: 250) 3 6 Enzymes hydolase 1 P84090 ERH Enhancer18-34 TYADYESVNECMEGVCK(SEQ ID 13 Uncategorized of rudimentary NO: 251)homolog P38117 ETFB Electron 36-51 HSMNPFCEIAVEEAVR 3 Channels, transfer(SEQ ID NO: 41) Transporters, flavoprotein Receptors subunit beta Q01844EQSR1 RNA- 269-292 QDHPSSMGVYGQESGGFSGPGEN 2 Transcriptionbinding protein R (SEQ ID NO: 252) factors, EWS Regulators Q9UQ84 EXO1139-160 SQGVDCLVAPYEADAQLAYLNK 13 2 Enzymes Exonuclease 1(SEQ ID NO: 95) 6 9 8 Q96CS3 FAF2 FAS- 249-277 LEGLIQPDDLINQLTFIMDANQTY6 Uncategorized associated factor LVSER (SEQ ID NO: 253) 2WEYVPLGPFLGK (SEQ ID NO:  14 Enzymes P16930 FAH 242-253 254)Fumarylacetoace tase Q9NRY5 FAM114A2 184-196 TMDVIAEGDPGFK (SEQ ID NO:14 Uncategorized Protein 255) FAM114A2 Q9NSD9 FARSB 72-82YDLLCLEGLVR (SEQ ID NO: 256) 9 Enzymes Phenylalanini-- tRNA ligasebeta subunit Q9NSD9 FARSB 518-530 IMQLLDVPPGEDK (SEQ ID NO:  2 EnzymesPhenylalanini-- 257) tRNA ligase beta subunit P49327 FASN Fatty1350-1383 GHPLGDIVAFLTSTEPQYGQGILS 14 13 Enzymes acid synthaseQDAWESLFSR (SEQ ID NO: 258) P37268 FDFT1 78-92ALDTLEDDMTISVEK (SEQ ID NO: 15 Enzymes Squalene 259) synthase P22830FECH 254-272 SEVVILFSAHSLPMSVVNR 4 Enzymes Ferrochelatase,(SEQ ID NOW: 42) mitochondrial O95684 FGFR1OP 39-50AAVFLALEEQEK (SEQ ID NO: 14 13 Adapter, FGFR1 260) 8 Scaffolding,oncogene Modulator partner Proteins Q96AY3 FKBP10 198-212GGTYDTYVGSGWLIK (SEQ ID 13 Enzymes Peptidyl-prolyl NO: 261) cis-transisomerase FKBP10 Q02790 FKBP4 190-206 FEIGEGENLDLPYGLER (SEQ ID 13Chaperones Peptidyl-prolyl NO: 262) cis-trans isomerase FKBP4 Q96AE4FUBP1 Far 593-620 MGQAVPAPTGAPPGGQPDYSAA 14 Transcription upstreamWAEYYR (SEQ ID NO: 263) factors, element-binding Regulators protein 1Q96AE4 FUBP1 Far 272-284 IGGNEGIDVPIPR (SEQ ID NO:  6 Transcriptionupstream 264) factors, element-binding Regulators protein 1 P35637FUS RNA- 335-348 GEATVSFDDPPSAK (SEQ ID NO:  2 Transcriptionbinding protein  265) factors, FUS Regulators P10253 GAA Lysosomal855-870 GELFWDDGESLEVLER (SEQ ID 9 Enzymes alpha- NO: 266) glucosidaseP50395 GDI2 Rab GDP 119-137 VPSTEAEALASSLMGLFEK (SEQ 13 14 Uncategorizeddissociation ID NO: 267) inhibitor beta P50395 GDI2 Rab GDP 222-240SPYLYPLYGLGELPQGFAR (SEQ 3 13 Uncategorized dissociation IN NO: 268)inhibitor beta Q9H3K2 GHITM Growth 218-240 AAWYTAGIVGGLSTVAMCAPSEK 14Uncategorized hormone- (SEQ ID NO: 269) inducible transmembrane proteinP06280 GLA Alpha- 241-252 SILDWTSFNQER 9 Enzymes galactosidase A(SEQ ID NO: 43) P06280 GLA Alpha- 68-82 LFMEMAELMVSEGWK 4 Enzymesgalactosidase A (SEQ ID NO: 45) P06280 GLA Alpha- 50-67FMCNLDCQEEPDSCISEK 9 Enzymes galactosidase A (SEQ ID NO: 44) P16278GLB1 Beta- 286-299 TEAVASSLYDILAR 9 Enzymes galactosidase(SEQ ID NO: 46) Q04760 GLO1 160-179 GLAFIQDPDGYWIEILNPNK 14 3 EnzymesLactoylglutathio (SEQ ID NO: 47) ne lyase Q9HC38 GLOD4 71-96TMVGFGPEDDHFVAELTYNYGV 4 13 Uncategorized GlyoxalaseGDYK (SEQ ID NO: 270) domain- containing protein 4 P00367 GLUD1 481-496HGGTIPIVPTAEFQDR 6 Enzymes Glutamate (SEQ ID NO: 49) dehydrogenase1, mitochondrial P00367 GLUD1 152-162 YSTDVSVDEVK 6 Enzymes Glutamate(SEQ ID NO: 48) dehydrogenase 1, mitochondrial P49448 GLUD2 152-162YSTDVSVDEVK 6 Enzymes Glutamate (SEQ ID NO: 48) dehydrogenase2, mitochondrial Q9H4A6 GOLPH3 Golgi 75-90 EGYTSFWNDCISSGLR 14 Adapter,phophoprotein (SEQ ID NO: 50) Scaffolding, 3 Modulator Proteins Q9BQ67GRWD1 183-198 LLQVVEEPQALAAFLR (SEQ ID 3 Uncategorized Glutamate-richNO: 271) WD repeat- containing protein 1 Q9BQ67 GRWD1 263-287SVEDLQWSPTENTVFASCSADASI 13 Uncategorized Glutamate-richR (SEQ ID NO: 272) WD repeat- containing protein 1 P09211 GSTP1 56-71FQDGDLTLYQSNTILR 2 Enzymes Glutathione S- (SEQ ID NO: 51)  transferase PP0C0S5 H2AFZ Histone 47-75 VGATAAVYSAAILEYLTAEVLEL 3 Transcription H2A.ZAGNASK (SEQ ID NO: 273) factors, Regulators Q16836 HADH 250-271LGAGYPMGPFELLDYVGLDTTK 13 2 Enzymes Hydroxyacyl- (SEQ ID NO: 274)coenzyme A dehydrogenase, mitochondrial P40939 HADHA 112-125TLQEVTQLSQEAQR (SEQ ID NO: 4 8 Enzymes Trifunctional 275) enzyme subunitalpha, mitochondrial P12081 HARS 170-193 EFYQCDFDIAGNFDPMIPDAECLK 15 14Enzymes Histidine--tRNA (SEQ ID NO: 276) 4 ligase, cytoplasmic Q96CS2HAUS1 HAUS 94-108 YLNALVDSAVALETK (SEQ ID 14 Adapter, augmin-likeNO: 277) Scaffolding, complex subunit Modulator 1 Proteins Q9NVX0HAUS2 HAUS 173-189 MDILVTETEELAENILK (SEQ ID 14 Adapter, augmin-likeNO: 278) Scaffolding, complex subunit Modulator 2 Proteins P69905 HBA218-32 VGAHAGEYGAEALER 4 Adapter, Hemoglobin (SEQ ID NO: 52) Scaffolding,subunit alpha Modulator Proteins P69905 HBA2 94-100 VDPVNFK 4 Adapter,Hemoglobin (SEQ ID NO: 53) Scaffolding, subunit alpha Modulator ProteinsP53701 HCCS 200-210 SWMGYELPFDE (SEQ ID NO: 279) 4 Enzymes Cytochrome c-type heme lyase Q7Z4Q2 HEATR3 HEAT 224-250 SFSATALNMLESALLSPVSSMESL 4 2Uncategorized repeat- LLK (SEQ ID NO: 280) containing protein 3 P06865HEXA Beta- 489-499 LTSDLTFAYER  9 Enzymes hexosaminidase (SEQ ID NO: 54)subuit alpha Q6NVY1 HIBACH 3- 238-252 ENIASVLENYHTESK (SEQ ID NO: 6Enzymes hydroxyisobutyr 281) yl-CoA hydrolase, mitochondrial P16403HIST1H1C 65-75 ALAAAGYDVEK (SEQ ID NO: 282) 8 Transcription Histone H1.2factors, Regulators P01892 HLA-A HLAC 46-59 FIAVGYVDDTQFVR (SEQ ID NO:14 Uncategorized class I 283) histocompatibility antigen, A-2 alphaQ8TCT9 HM13 Minor 62-73 NASDMPETITSR (SEQID NO: 284) 13 14 Enzymeshistocompatibility 2 4 8 antigen H13 P30519 HMOX2 Heme 48-55 AENTQFVK15 14 Enzymes oxygenase 2 (SEQ ID NO: 55) 3 4 2 6 8 P03519 HMOX2 Heme69-87 LATTALYFTYSALEEEMER 14 Enzymes oxygenase 2 (SEQ ID NO: 56) P09651HNRNPA1 353-370 NQGGYGGSSSSSSYGSGR (SEQ ID 13 14 Channels, HeterogeneousNO: 285) 3 2 9 Transporters, nuclear Receptors ribonucleoprotein A1P09651 HNRNPA1 337-350 SSGPYGGGGQYGAK (SEQ ID NO: 3 2 Channels,Heterogeneous 286) Transporters, nuclear Receptors ribonucleoprotein A1P09651 HNRNPA1 56-75 GFGFVTYATVEEVDAAMNAR 3 Channels, Heterogeneous(SEQ ID NO: 287) Transporters, nuclear Receptors ribonucleoprotein A1P09651 HNRNPA1 233-265 GGGGYGGSGDGYNGFGNDGGYG 8 Channels, HeterogeneousGGGPGYSGGSR (SEQ ID NO: 288) Transporters, nuclear Receptorsribonucleoprotein A1 P09651 HNRNPA1 16-31 LFIGGLSFETTDESLR (SEQ ID NO:14 3 2 Channels, Heterogeneous 289) Transporters, nuclear Receptorsribonucleoprotein A1 P09651 HNRNPA1 131-140 IEVIEIMTDR (SEQ ID NO: 290)3 9 8 Channels, Heterogeneous Transporters, nuclear Receptorsribonucleoprotein A1 Q32P51 HNRNPA1L2 285-298 SSGPYGGGGQYFAK (SEQ ID NO:3 2 4 Channels, Heterogeneous 291) Transporters, nuclear Receptorsribonucleoprotein A1-like 2 Q32P51 HNRNPA1L2 131-140IEVIEIMTDR (SEQ ID NO: 292) 3 4 9 Channels, Heterogeneous Transporters,nuclear Receptors ribonucleoprotein A1-like 2 Q32P51 HNRNPA1L2 16-31LFIGGLSFETTDESLR (SEQ ID NO: 14 3 4 Channels, Heterogeneous 293) 2Transporters, nuclear Receptors ribonucleoprotein A1-like 2 P22626HNRNPA2L1 130-137 DYFEEYGK (SEQ ID NO: 294) 6 Channels, HeterogeneousTransporters, nuclear Receptors ribonucleoproteins A2/B1 P22626HNRNPA2L1 138-147 IDTIEIITDR (SEQ ID NO: 295) 13 Channels, HeterogeneousTransporters, nuclear Receptors ribonucleoproteins A2/B1 P22626HNRNPA2L1 191-200 QEMQEVQSSR (SEQ ID NO: 296) 6 Channels, HeterogeneousTransporters, nuclear Receptors ribonucleoproteins A2/B1 P22626HNRNPA2L1 229-238 GGSDGYGSGR (SEQ ID NO: 297) 3 6 Channels,Heterogeneous Transporters, nuclear Receptors ribonucleoproteins A2/B1P22626 HNRNPA2L1 239-266 GFGDGYNGYGGGPGGGNFGGSP 13 14 Channels,Heterogeneous GYGGGR (SEQ ID NO: 298) 3 2 6 Transporters, nuclear 8Receptors ribonucleoproteins A2/B1 P22626 HNRNPA2L1 23-38LFIGGLSFETTEESLR (SEQ ID NO: 13 3 2 Channels, Heterogeneous 299) 6 9Transporters, nuclear Receptors ribonucleoproteins A2/B1 P22626HNRNPA2L1 267-317 GGYGGGGPGYGNQGGGYGGGY 13 2 Channels, HeterogeneousDNYGGGNYGSGNYNDFGNYNQQ 9 6 Transporters, nuclearPSNYPGMK (SEQ ID NO: 300) Receptors ribonucleoproteins A2/B1 P22626HNRNPA2L1 326-350 NMGGPYGGGNYGPGGSGGSGGY 14 3 2 Channels, HeterogeneousGGR (SEQ ID NO: 301) 13 8 6 Transporters, nuclear Receptorsribonucleoproteins A2/B1 P22626 HNRNPA2L1 42472TLETVPLER (SEQ ID NO: 302) 6 Channels, Heterogeneous Transporters,nuclear Receptors ribonucleoproteins A2/B1 P51991 HNRNPA3 152-161IETIEVMEDR (SEQ ID NO: 303) 9 6 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein A3 SSGSPYGGGYGSGGGSGGYGSR 13 14Transcription P51991 HNRNPA3 355-376 (SEQ ID NO: 304) 3 2 4 factors,Heterogeneous 6 Regulators nuclear ribonucleoprotein A3 P51991 HNRNPA337-52 LFIGGLSFETTDDSLR (SEQ ID NO: 4 Transcription Heterogeneous 305)factors, nuclear Regulators ribonucleoprotein A3 P07910 HNRNP C 100-130SAAEMYGSVTEHPSPSPLLSSSFD 13 4 Transcription HeterogeneousLDYDFQR (SEQ ID NO: 306) factors, nuclear Regulators ribonucleoproteinsC1/C2 P07910 HNRNPC 136-142 MYSYPAR (SEQ ID NO: 307) 4 3 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoproteins C1/C2P07910 HNRNP C 51-61 GFAFVQVYVNER  2 13 Transcription Heterogeneous(SEQ ID NO: 308) factors, nuclear Regulators ribonucleoproteins C1/C2P07910 HNRNPC 65-73 AAVAGEDGR (SEQ ID NO: 309) 4 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoproteins C1/C2P07910 HNRNP C 74-89 MIAGQVLDINLAAEPK (SEQ ID 4 3 2 TranscriptionHeterogeneous NO: 310) 13 factors, nuclear Regulators ribonucleoproteinsC1/C2 Q14103 HNRNP D 184-197 IFVGGLSPDTPEEK (SEQ ID NO: 13 6Transcription Heterogeneous 311) factors, nuclear Regulatorsribonucleoprotein D0 P52597 HNRNPF 151-167 ITGEAFVQFASQELAEK (SEQ ID4 2 13 Transcription Heterogeneous NO: 312) 9 factors, nuclearRegulators ribonucleoprotein F P52597 HNRNPF 53-68QSGEAFVELGSEDDVK (SEQ ID 6 Transcription Heterogeneous NO: 313) factors,nuclear Regulators ribonucleoprotein F P52597 HNRNP F 99-114HSGPNSADSANDGFVR (SEQ ID 6 Transcription Heterogeneous NO: 314) factors,nuclear Regulators ribonucleoprotein F P52597 HNRNPF 125-150EEIVQFFSGLEIVPNGITLPVDPEG 3 6 Transcription HeterogeneousK (SEQ ID NO: 315) factors, nuclear Regulators ribonucleoprotein FP52597 HNRNP F 300-316 ATENDIYNFFSPLNPVR (SEQ ID 13 3 2 TranscriptionHeterogeneous NO: 316) 4 6 factors, nuclear Regulators ribonucleoproteinF P52597 HNRNPF 317-326 VHIEIGPDGR (SEQ ID NO: 317) 6 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoprotein F P31943HNRNPH1 125-150 EEIVQFFSGLEIVPNGITLPVDFQG 2 6 TranscriptionHeterogeneous R (SEQ ID NO: 318) factors, nuclear Regulatorsribonucleoprotein H P31943 HNRNPH1 151-167 STGEAFVQFASQEIAEK (SEQ ID13 14 Transcription Heterogeneous NO: 319) 3 6 8 factors, nuclearRegulators ribonucleoprotein H P31943 HNRNPH1 234-259GAYGGGYGGYDDYNGYNDGYG 3 2 13 Transcription HeterogeneousFGSDR (SEQ ID NO: 320) 6 8 factors, nuclear Regulators ribonucleoproteinH P31943 HNRNPH1 263-275 DLNYCFSGMSDHR (SEQ ID NO: 6 TranscriptionHeterogeneous 321) factors, nuclear Regulators ribonucleoprotein HP31943 HNRNPH1 276-294 YGDGGSTFQSTTGHCVHMR (SEQ 6 TranscriptionHeterogeneous ID NO: 322) factors, nuclear Regulators ribonucleoproteinH P31943 HNRNPH1 300-316 ATENDIYNFFSPLNPVR (SEQ ID 13 14 TranscriptionHeterogeneous NO: 323) 3 2 6 factors, nuclear Regulatorsribonucleoprotein H P31943 HNRNPH1 317-326 VHIEIGPDGR (SEQ ID NO: 324)3 6 Transcription Heterogeneous factors, nuclear Regulatorsribonucleoprotein H P31943 HNRNPH1 356-375 YVELFLNSTAGASGGAYEHR 3 6Transcription Heterogeneous (SEQ ID NO: 325) factors, nuclear Regulatorsribonucleoprotein H P31943 HNRNPH1 99-114 HTGPNSPDTANDGFVR (SEQ ID 6Transcription Heterogeneous NO: 326) factors, nuclear Regulatorsribonucleoprotein H P55795 HNRNPH2 151-167 STGEAFVQFASQEIAEK (SEQ ID13 14 Transcription Heterogeneous NO: 327) 3 8 6 factors, nuclearRegulators ribonucleoprotein H2 P55795 HNRNPH2 234-259GAYGGGYGGYDDYGGYNDGYG 8 6 Transcription HeterogeneousFGSDR (SEQ ID NO: 328) factors, nuclear Regulators ribonucleoprotein H2P55795 HNRNPH2 263-275 DLNYCFSGMSDHR (SEQ ID NO: 6 TranscriptionHeterogeneous 329) factors, nuclear Regulators ribonucleoprotein H2P55795 HNRNPH2 300-316 ATENDIYNFFSPLNPMR (SEQ ID 6 TranscriptionHeterogeneous NO: 330) factors, nuclear Regulators ribonucleoprotein H2P55795 HNRNPH2 317-326 VHIEIGPDGR (SEQ ID NO: 331) 6 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoprotein H2 P55795HNRNPH2 99-114 HTGPNSPDTANDGFVR (SEQ ID  6 Transcription HeterogeneousNO: 332) factors, nuclear Regulators ribonucleoprotein H2 P31942 HNRNPH3139-169 GGDGYDGGYGGFDDYGGYNNY 6 Transcription HeterogeneousGYGNDGFDDR (SEQ ID NO: 333) factors, nuclear Regulatorsribonucleoprotein H3 P31942 HNRNPH3 206-222 ATENDIANFFSPLNPIR (SEQ ID2 4 6 Transcription Heterogeneous NO: 334) factors, nuclear Regulatorsribonucleoprotein H3 P31942 HNRNPH3 262-287 YIELFLNSTPGGGSGMGGSGMGG14 4 2 Transcription Heterogeneous YGR (SEQ ID NO: 335) 6 factors,nuclear Regulators ribonucleoprotein H3 P31942 HNRNPH3 288-301DGMDNQGGYGSVGR (SEQ ID 8 6 Transcription Heterogeneous NO: 336) factors,nuclear Regulators ribonucleoprotein H3 P31942 HNRNPH3 324-343GGGGSGGYYGQGGMSGGGWR 2 Transcription Heterogeneous (SEQ ID NO: 337)factors, nuclear Regulators ribonucleoprotein H3 P31942 HNRNPH3 56-67STGEAFVQFASK  6 Transcription Heterogeneous (SEQ ID NO: 338) factors,nuclear Regulators ribonucleoprotein H3 P61978 HNRNP K 423-433IDEPLEGSEDR (SEQ ID NO: 339) 4 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein K P61978 HNRNPK 397-405DLAGSIIGK (SEQ ID NO: 340) 4 3 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein K P61978 HNRNPK 415-422HESGASIK (SEQ ID NO: 341) 4 3 13 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein K P61978 HNRNP K 434-456IITITGTQDQIQNAQYLLQNSVK 13 14 Transcription Heterogeneous(SEQ ID NO: 342) 3 2 4 factors, nuclear 9 8 Regulators ribonucleoproteinK P61978 HNRNPK 70-86 TDYNASVSVPDSSGPER (SEQ ID 8 4 TranscriptionHeterogeneous NO: 343) factors, nuclear Regulators ribonucleoprotein KP61978 HNRNP K 87-102 ILSISADIETIGEILK (SEQ ID NO: 4 TranscriptionHeterogeneous 344) factors, nuclear Regulators ribonucleoprotein KP61978 HNRNPK 104-139 IIPTLEEGLQLPSPTATSQLPLESDA 13 14 TranscriptionHeterogeneous VECLNYQHYK (SEQ ID NO: 345) 3 4 2 factors, nuclearRegulators ribonucleoprotein K P61978 HNRNP K 180-191 LFQECCPHSTDR  13Transcription Heterogeneous (SEQ ID NO: 346) factors, nuclear Regulatorsribonucleoprotein K P61978 HNRNPK 208-219 IILDLISESPIK  14 4 2Transcription Heterogeneous (SEQ ID NO: 347) 13 9 factors, nuclearRegulators ribonucleoprotein K P61978 HNRNP K 222-246AQPYDPNFYDETYDYGGFTMMF 4 Transcription HeterogeneousDDR (SEQ ID NO: 348) factors, nuclear Regulators ribonucleoprotein KP61978 HNRNPK 279-286 DYDDMSPR (SEQ ID NO: 349) 4 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoprotein K P61978HNRNP K 317-325 GGDLMAYDR (SEQ ID NO: 350) 2 Transcription Heterogeneousfactors, nuclear Regulators ribonucleoprotein K P61978 HNRNPK 378-396GSYGDLGGPIITTQVTIPK (SEQ ID 14 3 2 Transcription Heterogeneous NO: 351)4 13 9 factors, nuclear 8 Regulators ribonucleoprotein K P14866 HNRNP L108-136 GLIDGVVEADLVEALQEFGPISYV 14 3 9 Transcription HeterogeneousVVMPK (SEQ ID NO: 352) factors, nuclear Regulators ribonucleoprotein LP14866 HNRNPL 399-411 VFNVFCLYGNVEK (SEQ ID NO: 2 TranscriptionHeterogeneous 353) factors, nuclear Regulators ribonucleoprotein LP14866 HNRNPL 47-56 YYGGGSEGGR (SEQ ID NO: 354) 3 TranscriptionHeterogeneous factors, nuclear Regulators ribonucleoprotein L P52272HNRNPM 346-362 MGGMEGPFGGGMENMGR (SEQ 14 2 6 Transcription HeterogeneousID NO: 355) factors, nuclear Regulators ribonucleoprotein M P52272HNRNPM 532-543 MVPAGMGAGLER (SEQ ID NO:  6 Transcription Heterogeneous356) factors, nuclear Regulators ribonucleoprotein M P52272 HNRNPM202-214 LGSTVFVANLDYK (SEQ ID NO: 6 Transcription Heterogeneous 357)factors, nuclear Regulators ribonucleoprotein M P52272 HNRNPM 323-345GIGMGNIGPAGMGMEGIGFGINK 3 2 6 Transcription Heterogeneous(SEQ ID NO: 358) factors, nuclear Regulators ribonucleoprotein M P52272HNRNPM 437-443 MGLVMDR(SEQ ID NO: 359) 6 Transcription Heterogeneousfactors, nuclear Regulators ribonucleoprotein M P52272 HNRNPM 457-471MGPLGLDHMASSIER (SEQ ID  3 6 Transcription Heterogeneous NO: 360)factors, nuclear Regulators ribonucleoprotein M P52272 HNRNPM 544-550MGPVMDR (SEQ ID NO: 361) 6 Transcription Heterogeneous factors, nuclearRegulators ribonucleoprotein M P52272 HNRNPM 551-557MATGLER (SEQ ID NO: 362) 6 Transcription Heterogeneous factors, nuclearRegulators ribonucleoprotein M P52272 HNRNPM 571-578MGANSLER (SEQ ID NO: 363) 6 Transcription Heterogeneous factors, nuclearRegulators ribonucleoprotein M P52272 HNRNPM 592-606MGPAMGPALGAGIER (SEQ ID 2 6 Transcription Heterogeneous NO: 364)factors, nuclear Regulators ribonucleoprotein M P52272 HNRNPM 699-707FESPEVAER (SEQ ID NO: 365) 6 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein M P52272 HNRNPM 95-110VGEVTYVELLMDAEGK (SEQ ID 13 14 Transcription Heterogeneous NO: 366)3 2 6 factors, nuclear 9 Regulators ribonucleoprotein M P52272 HNRNPM113-120 GCAVVEFK (SEQ ID NO: 367) 6 Transcription Heterogeneous factors,nuclear Regulators ribonucleoprotein M P52272 HNRNPM 486-496MGAGMGFGLER (SEQ ID NO:  6 Transcription Heterogeneous 368) factors,nuclear Regulators O43390 HNRNPR 147-171 YGGPPPDSVYSGVQPGIGTEVFVG 6Transcription Heterogeneous K (SEQ ID NO: 369) factors, nuclearRegulators ribonucleoprotein R O43390 HNRNPR 316-339VWGNVVTVEWADPVEEPDPEVM 6 Transcription Heterogeneous AK (SEQ ID NO: 370)factors, nuclear Regulators ribonucleoprotein R O43390 HNRNPR 347-359NLATTVTEEILKE (SEQ ID NO:  6 Transcription Heterogeneous 371) factors,nuclear Regulators ribonucleoprotein R O43390 HNRNPR 428-441STAYEDYYYHPPPR (SEQ ID NO: 2 6 Transcription Heterogeneous 372) factors,nuclear Regulators ribonucleoprotein R Q99714 HSD17B10 3- 42672GLVAVITGGASGLGLATAER 3 2 Enzymes hydroxyacyl- (SEQ ID NO: 373) CoAdehydrogenase type-2 Q53GQ0 HSD17B12 182-206 GAILNISSGSGMLPVPLLTIYSATK14 2 Enzymes Estradio 17- (SEQ ID NO: 374) beta- dehydrogenase 12 Q53GQ0HSD17B12 36-64 VWGVGNEAGVGPGLGEQAVVT 14 4 2 Enzymes Estradio 17-GSTDGIGK (SEQ ID NO: 375) beta- dehydrogenase 12 P51659 HSD17B4 169-183LGLLGLANSLAIEGR 3 Enzymes Peroxisomal (SEQ ID NO: 57) multifunctionalenzyme type 2 P51659 HSD17B4 385-403 SMMGGGLAEIPGLSINFAK (SEQ 14 EnzymesPeroxisomal ID NO: 376) multifunctional enzyme type 2 P51659 HSD17B4622-633 LQSTFVFEEIGR  14 Enzymes Peroxisomal (SEQ ID NO: 377)multifunctional enzyme type 2 P07900 HSP90AA1 368-386VFIMDNCEELIPEYLNFIR (SEQ ID 13 Chaperones Heat shock NO: 378)protein HSP 90- alpha P07900 HSP90AA1 300-314NPDDITNEEYGEFYK (SEQ ID NO:  13 Chaperones Heat shock 379)protein HSP 90- alpha P07900 HSP90AA1 514-534 HGLEVIYMIERPIDEYCVQQLK 13Chaperones Heat shock (SEQ ID NO: 380) protein HSP 90- alpha P08238HSP90AB1 360-378 VFIMDSCDELIPEYLNFIR 14 13 Chaperones Heat shock(SEQ ID NO: 58) protein HSP 90- beta P08238 HSP90AB1 507-526GFEVVYMTEPIDEYCVQQLK 13 14 Chaperones Heat shock (SEQ ID NO: 59)protein HSP 90- beta P08238 HSP90AB1 686-719 LGLGIDEDEVAAEEPNAAVPDEIP13 14 Chaperones Heat shock PLEGDEDASR (SEQ ID NO: 381) protein HSP 90-beta P14625 HSP90B1 664-671 AQAYQTGK (SEQ ID NO: 382) 13 8 ChaperonesEndoplasmin P14625 HSP90B1 117-135 LISLTDENALSGNEELTVK 9 ChaperonesEndoplasmin (SEQ ID NO: 60) P14625 HSP90B1 271-285 YSQFINFPIYVWSSK 6Chaperones Endoplasmin (SEQ ID NO: 61) P14625 HSP90B1 495-503LGVIEDHSNR (SEQ ID NO: 383) 6 Chaperones Endoplasmin P14625 HSP90B152-67 EEEAIQLDGLNASQIR (SEQ ID 6 Chaperones Endoplasmin NO: 384) P08107HSPA1B Heat 113-126 AFYPEEISSMVLTK (SEQ ID NO: 13 Chaperonesshock 70 kDa 385) protein 1A/1B P08107 HSPA1B Heat 176-187IINEPTAAAIAYGLDR (SEQ ID NO: 13 Chaperones shock 70 kDa 386)protein 1A/1B P08107 HSPA1B Heat 362-384 SINPDEAVAYGAAVQAAILMGDK 13Chaperones shock 70 kDa (SEQ ID NO: 387) protein 1A/1B P08107HSPA1B Heat 424-447 QTQIFTTYSDNQPGVLIQVYEGER 13 3 Chaperonesshock 70 kDa (SEQ ID NO: 388) protein 1A/1B P08107 HSPA1B Heat 598-628ELEQVCNPIISGLYQGAGGPGPGG 13 Chaperones shock 70 kDaFGAQGPK (SEQ ID NO: 389) protein 1A/1B P11021 HSPA5 78 kDa 602-617IEWLESHQDADIEDFK (SEQ ID 6 Chaperones glucose- NO: 390)regulated protein P11021 HSPA5 78 kDa 82-96 NQLTSNPENTVFDAK (SEQ ID 9 6Chaperones glucose- NO: 391) regulated protein P11021 HSPA5 78 kDa475-492 DNHLLGTFDLTGIPPAPR (SEQ ID 6 Chaperones glucose- NO: 392)regulated protein P11021 HSPA5 78 kDa 61-74 ITPSYVAFTPEGER (SEQ ID NO: 6Chaperones glucose- 393) regulated protein P11142 HSPA8 Heat 424-447QTQTFTTYSDNQPGVLIQVYEGER 13 14 Chaperones shock cognate (SEQ ID NO: 394)71 kDa protein P11142 HSPA8 Heat 113-126 SFYPEEVSSMVLTK 13 14 Chaperonesshock cognate (SEQ ID NO: 62) 71 kDa protein P38646 HSPA9 Stress-266-284 STNGDTFLGGEDFDQALLR (SEQ 13 8 Chaperones 70 protein, ID NO: 395)mitochondrial P10809 HSPD1 60 kDA 345-352 VGEVIVTK (SEQ ID NO: 396) 3Chaperones heat shock protein,  mitochondrial P10809 HSPD1 60 kDA206-218 TLNDELEIIEGMK (SEQ ID NO: 13 3 Chaperones heat shock 397)protein,  mitochondrial P10809 HSPD1 60 kDA 222-233 GYISPYGINTSK  13Chaperones heat shock (SEQ ID NO: 398) protein,  mitochondrial P10809HSPD1 60 kDA 251-268 ISSIQSIVPALEIANAHR (SEQ ID 3 13 Chaperonesheat shock NO: 399) protein,  mitochondrial P10809 HSPD1 60 kDA 371-387IQEIIEQLDVTTSEYEK (SEQ ID 13 Chaperones heat shock NO: 400) protein, mitochondrial P10809 HSPD1 60 kDA 494-516 IMQSSSEGYDAMAGDFVNMVE 13 8Chaperones heat shock K (SEZ ID NO: 401) protein,  mitochondrial P10809HSPD1 60 kDA 97-121 LVQDVANNTNEEAGDGTTTATVL 13 8 Chaperones heat shockAR (SEQ ID NO: 402) protein,  mitochondrial HSPD1 60 kDA Q9NSE4 IARS2818-832 SCQTALVEILDVIVR (SEQ ID NO: 14 3 2 Enzymes Isoleucine-- 403)13 6 tRNA ligase, mitochondrial Q9NSE4 IARS2 793-803ELSNFYFSIIK (SEQ ID NO: 404) 2 6 Enzymes Isoleucine-- tRNA ligase,mitochondrial P14735 IDE Insulin- 312-324 NLYVTFPIPDLQK (SEQ ID NO:  4Enzymes degrading 405) enzyme P48735 IDH2 Isocitrate 244-251WPLYMSTK (SEQ ID NO: 406) 3 6 Enzymes dehydrogenase P13284 IFI30 Gamma-129-157 VEACVLDELDMELAFLTIVCMEE 9 Enzymes interferon-FEDMER (SEQ ID NO: 407) inducible lysosomal thiol reductase Q9NZI8IGF2BP1 509-525 TVNELQNLTAAEVVVPR (SEQ ID 3 13 Channels, Insulin-likeNO: 408) Transporters, growth factor 2 Receptors mRNA-binding proteinQ12905 ILF2 Interleukin 329-356 ILGQEGDASYLASEISTWDGVIVT 4 Transcriptionenhancer- PSE (SEQ ID NO: 409) factors, binding factor 2 RegulatorsQ12905 ILF2 Interleukin 81-103 INNVIDNLIVAPGTFEVQIEEVR 13 4Transcription enhancer- (SEQ ID NO: 410) factors, binding factor 2Regulators AIL0T0 ILVBL 557-577 EQVPSLGSNVACGLAYTDYHK 13 EnzymesAcetolactate (SEQ ID NO: 411) synthase-like protein Q16891 IMMT 345-353VQAAQSEAK (SEQ ID NO: 412) 4 3 6 Uncategorized Mitochondrialinner membrane protein Q16891 IMMT 527-545 LSQEQVDNFTLDINTAYAR (SEQ13 14 Uncategorized Mitochondrial ID NO: 413) 6 8 inner membrane proteinQ16891 IMMT 548-564 GIEQAVAQSHAVAEEEAR (SEQ ID 13 4 6 UncategorizedMitochondrial NO: 414) inner membrane protein P12268 IMPDH2 110-124YEQGFITDPVVLSPK 13 Enzymes Inosine-5- (SEQ ID NO: 63) monophosphatedehydrogenase 2 Q8TEX9 IPO4 Importin-4 163-182 LLNETLGEVGSPGLLFYSLR (SEQ4 Channels, ID NO: 415) Transporters, Receptors O00410 IPO5 Importin-5721-735 VAAAESMPLLLECAR (SEQ ID 14 2 Channels, NO: 416) 13 8Transporters, Receptors O95373 IPO7 Importin-7 441-427TMGFCYQILTEPNADRP (SEQ ID 13 Channels, NO: 417) Transporters, ReceptorsQ96P70 IPO9 Importin-9 49-74 VLEVTEEFGVHLAELTVDPQGAL 14 Channels,AIR (SEQ ID NO: 418) Transporters, Receptors O14654 IRS4 Insulin 256-267LCLTDEEVVFVR (SEQ ID NO:  14 Uncategorized receptor 419) substrate 4Q92945 KHSRP Far 629-646 IGQQPQQPGAPPQQDYTK (SEQ ID 2 6 Transcriptionupstream NO: 420) factors, element-binding Regulators dehydrogenase 2P52732 KIF11 Kinesin- 158-181 VSLLEIYNEELFDLLNPSSDVSER 6 Adapter,like protein (SEQ ID NO: 421) Scaffolding, KIF11 Modulator ProteinsP52292 KPNA2 203-227 YGAVDPLLALLAVPDMSSLACGY 14 13 Channels,Importin subunit LR (SEQ ID NO: 422) Transporters, alpha-2 ReceptorsP52292 KPNA2 301-315 LLGASELPIVTPALR (SEQ ID NO:  13 Channels,Importin subunit 423) Transporters, alpha-2 Receptors Q14974 KPNB1317-332 GALQYLVPILTQTLTK (SEQ ID 14 13 Channels, Importin subunitNO: 424) Transporters, beta-1 Receptors Q14974 KPNB1 28-42AAVENLPTFLVELSR (SEQ ID NO: 14 13 Channels, Importin subunit 425)Transporters, beta-1 Receptors Q14974 KPNB1 526-537 SSAYESLMEIVK  13 14Channels, Importin subunit (SEQ ID NO: 426) Transporters, beta-1Receptors P13473 LAMP2 133-144 GILTVDELLAIR  14 9 UncategorizedLysosome- (SEQ ID NO: 427) associated membrane glycoprotein 2 Q9P2J5LARS Leucine-- 1007-1017 ILDLQLEFDEK (SEQ ID NO: 428) 13 EnzymestRNA ligase, cytoplasmic P00338 LDHA L-lactate 43-57 DLADELALVDVIEDK 9Enzymes dehydrogenase (SEQ ID NO: 64) A chain P07195 LDHB L-lactate234-244 MVVESAYEVIK 4 Enzymes dehydrogenase (SEQ ID NO: 65) B chainO95202 LETM1 LETM1 452-463 VAEVEGEQVDNK (SEQ ID NO: 13 14 Uncategorizedand EF-hand 429) 4 3 8 domain- containing protein 1, mit Q08380 LGALS3BP522-541 ALMLCEGLFVADVTDFEGWK 9 Uncategorized Galectin-3-(SEQ ID NO: 430) binding protein Q99538 LGMN 102-118 DYTGEDVTPQNFLAVLR 9Enzymes Legumain (SEQ ID NO: 66) P38571 LIPA 255-270ELCGNLCFLLCGFNER (SEQ ID 14 Enzymes Lysosomal acid NO: 431)lipase/cholestery 1 ester hydrolase P02545 LMNA 63-72ITESEEVVSR (SEQ ID NO: 432) 6 Uncategorized Prelamin-A/C P02545 LMNA172-180 LEAALGEAK (SEQ ID NO: 433) 3 Uncategorized Prelamin-A/C P02545LMNA 209-216 NIYSEELR (SEQ ID NO: 434) 6 Uncategorized Prelamin-A/CP02545 LMNA 281-296 NSNLVGAAHEELQQSR (SEQ ID 6 UncategorizedPrelamin-A/C NO: 435) P02545 LMNA 352-366 MQQQLDEYQELLDIK 13 6Uncategorized Prelamin-A/C (SEQ ID NO: 96) P20700 LMNB1 Lamin- 321-330IQELEDLLAK (SEQ ID NO: 436) 6 Uncategorized B1 P20700 LMNB1 Lamin- 80-90ALYETELADAR (SEQ ID NO: 437) 13 Uncategorized B1 P20700 LMNB1 Lamin-351-367 DQMQQQLNDYEQLLDVK (SEQ 14 8 Uncategorized B1 ID NO: 438) P20700LMNB1 Lamin- 210-220 SMYEEEINETR (SEQ ID NO: 439) 13 Uncategorized B1P20700 LMNB1 Lamin- 52-67 SLETENSALQLQVTER (SEQ ID 13 14 UncategorizedB1 NO: 440) 6 8 Q03252 LMNB2 Lamin- 106-113 AELDEVNK (SEQ ID NO: 441) 6Uncategorized B2 Q03252 LMNB2 Lamin- 74-84 ALYESELADAR (SEQ ID NO: 442)13 Uncategorized B2 Q03252 LMNB2 Lamin- 139-150 SEVELAAALSDK (SEQ ID NO:13 Uncategorized B2 443) P36776 LONP1 Lon 598-632GYQGDPSSALLELLDPEQNANFL 13 6 Channels, protease DHYLDVPVDLSK (SEQ ID NO:Transporters, homolog, 444) Receptors mitochondrial Q96AG4 LRRC59268-292 VTELQQQPLCTSVNTIYDNAVQG 13 14 Uncategorized Leucine-richLR (SEQ ID NO: 445) 2 8 repeat- containing protein 59 P09960 LTA4H366-386 LVVDLTDIDPDVAYSSVPYEK 13 4 8 Enzymes Leukotriene A-4(SEQ ID NO: 67) hydrolase O00754 MAN2B1 291-305 ELVDYFLNVATAQGR (SEQ ID 14 Enzymes Lysosomal NO: 446) alpha- mannosidase O00754 MAN2B1 614-638ATFDPDTGLLMEIMNMNQQLLLP 9 Enzymes Lysosomal VR (SEQ ID NO: 447) alpha-mannosidase Q9Y2E5 MAN2B2 642-664 AAVPAWEAVEMEIVAGQLVTEIR 9 EnzymesEpididymis (SEQ ID NO: 448) specific alpha- mannosidase Q15691 MAPRE1223-241 NIELICQENEGENDPVLQR (SEQ 13 Adapter, Microtubule- ID NO: 449)Scaffolding, associated Modulator protein RP/EB Proteins family memberQ8NI22 MCFD2 103-126 EEGSEQAPLMSEDELINIIDGVLR 14 Channels, Multiple(SEQ ID NO: 450) Transporters, coagulation Receptors factor deficiencyprotein 2 P49736 MCM2 DNA 797-807 VMLESFIDTQK (SEQ ID NO: 451) 13Transcription replication factors, licensing factor Regulators MCM2P33991 MCM4 DNA 502-516 AEINILLCGDPGTSK (SEQ ID NO: 15 Transcriptionreplication 452) factors, licensing factor Regulators MCM4 P33991MCM4 DNA 517-529 SQLLQYVYNLVPR (SEQ ID NO: 6 Transcription replication453) factors, licensing factor Regulators MCM4 Q14566 MCM6 DNA 59-85NTLVVSFVDLEQFNQQLSTTIQEE 14 15 Transcription replicationFYR (SEQ ID NO: 454) 3 6 factors, licensing factor Regulators MCM6Q14696 MESDC2 LDLR 113-127 TLMMFVTVSGSPTEK (SEQ ID 2 Chaperoneschaperone NO: 455) MESD Q9H8H3 METTL7A 94-105 VTCIDPNPNFEK  13 EnzymesMethyltransferase- (SEQ ID NO: 456) like protein 7A P46013 MKI67 Anitgen648-659 SGASEANLIVAK  8 Transcription KI-67 (SEQ ID NO: 457) factors,Regulators Q7Z7F7 MRPL55 39S 59-67 QDGSTIHIR (SEQ ID NO: 458) 6Uncategorized ribosomal protein L55, mitochondrial P43246 MSH2 DNA848-871 ALELEEFQYIGESQGYDIMEPAAK 14 Transcription mismathc repair(SEQ ID NO: 459) factors, protein Msh2 Regulators P00403 MT-CO2 142-151VVLPIEAPIR (SEQ ID NO: 460) 6 Channels, Cytochrome c Transporters,oxidase subunit Receptors 2 P03891 MT-ND2 264-272WAIIEEFTK (SEQ ID NO: 461) 14 Enzymes NADH- ubiquinone oxidoreductasechain 2 Q9NZJ7 MTCH1 65-103 MDGGSGGLGSGDNAPTTEALFVA 14 2 Channels,Mitochondrial LGAGVTALSHPLLYVK (SEQ ID Transporters, carrier homologNO: 462) Receptors 1 Q86UE4 MTDH Protein 42510 SWQDELAQQAEEGSAR (SEQ ID14 4 2 Uncategorized LYRIC NO: 463) 13 8 Q86UE4 MTDH Protein 34-45TELGLDGLEPK (SEQ ID NO: 464) 13 14 Uncategorized LYRIC 4 2 9 8 Q9UDX5MTFP1 21-33 YLGYANEVGEAFR (SEQ ID NO:  13 14 Uncategorized Mitochondrial465) 2 9 fission process protein 1 Q9UDX5 MTFP1 103-116VCAASLYVLGTATR (SEQ ID NO: 14 Uncategorized Mitochondrial 466)fission process protein 1 Q6UB35 MTHFD1L 307-326IHFGGLIEEDDVILLAAALR (SEQ 6 Enzymes Monofunctional ID NO: 467) C1-tetrahydrofolate synthase, mitochondrial Q13505 MTX1 Metaxin- 238-252QGADTLAFMSLLEEK (SEQ ID 14 3 4 Channels, 1 NO: 468) 2 6 8 Transporters,Receptors P35580 MYH10 1546-1562 TQLEELEDELQATEDAK (SEQ ID 13 6 Adapter,Myosin-10 NO: 469) 9 Scaffolding, Modulator Proteins P35580 MYH101684-1701 SLEAEILQLQEELASSER (SEQ ID 14 13 Adapter, Myosin-10 NO: 470) 6Scaffolding, Modulator Proteins P35580 MYH10 1738-1758IAQLEEELEEEQSNMELLNDR 6 Adapter, Myosin-10 (SEQ ID NO: 471) Scaffolding,Modulator Proteins P35580 MYH10 1814-1822 ATISALEAK (SEQ ID NO: 472) 6Adapter, Myosin-10 Scaffolding, Modulator Proteins P35580 MYH10 248-268INFDVTGYIVGANIETYLLEK 6 9 Adapter, Myosin-10 (SEQ ID NO: 473)Scaffolding, Modulator Proteins P35580 MYH10 890-910NILAEQLQAETELFAEAEEMR 13 14 Adapter, Myosin-10 (SEQ ID NO: 474) 6 9Scaffolding, Modulator Proteins P35579 MYH9 Myosin- 1539-1555TQLEELEDELQATEDAK (SEQ ID 13 Adapter, 9 NO: 475) Scaffolding, ModulatorProteins P35579 MYH9 Myosin- 1677-1694 SMEAEMIQLQEELAAAER (SEQ 13Adapter, 9 ID NO: 476) Scaffolding, Modulator Proteins Q9BXJ9 NAA15 N-798-818 NLQTCMEVLEALYDGSLGDCK 14 4 2 Transcription alpha-(SEQ ID NO: 477) factors, acetyltransferase Regulators 15, NatAauxiliary subunit 566-580 QAVQELVSLYYEEAR (SEQ ID 9 Enzymes P54802NAGLU Alpha- NO: 478) N- acetylglucosami nidase P54802 NAGLU Alpha-594-615 AGGVLAYELLPALDEVLASDSR 13 15 Enzymes N- (SEQ ID NO: 479)acetylglucosami nidase P43490 NAMPT 175-189 YLLETSGNLDGLEYK 13 14Enzymes Nicotinamide (SEQ ID NO: 68) 15 3 6 phosphoribosyltr 8 ansferaseP55209 NAP1L1 95-104 FYEEVHDLER (SEQ ID NO: 480) 3 4 13 UncategorizedNucleosome 6 9 8 assembly protein 1-like 1 P55209 NAP1L1 177-194NVDLLSDMVQEHDEPILK (SEQ 6 Uncategorized Nucleosome ID NO: 481)assembly protein 1-like 1 P55209 NAP1L1 56-72 LDGLVETPTGYIESLPR (SEQ ID14 4 2 Uncategorized Nucleosome NO: 482) 9 assembly protein 1-like 1Q99733 NAP1L14 84-93 FYEEVHDLER (SEQ ID NO: 483) 3 4 13 UncategorizedNucleosome 6 9 8 assembly protein 1-like 4 P49321 NASP Nuclear 503-526SLQENEEEEIGNLELAWDMLDLA 13 14 Channels, autoantigenic K (SEQ ID NO: 484)8 Transporters, sperm protein Receptors P49321 NASP Nuclear 77-93YGETANECGEAFFFYGK (SEQ ID  13 Channels, autoantigenic MO: 485)Transporters, sperm protein Receptors Q9H0A0 NAT10 N- 600-625ASGDLIPWTVSEQFQDPDFGGLSG 13 3 Enzymes acetyltransferaseGR (SEQ ID NO: 486) 10 Q08161 NCBP1 Nuclear 42-65SACSLESNLEGLAGVLEADLPNY 13 14 Channels, cap-binding K (SEQ ID NO: 487)3 2 Transporters, protein subunit 1 Receptors P28331 NDUFS1 312-325GLLTYTSWEDALSR (SEQ ID NO:  14 Enzymes NADH- 488) ubiquinoneoxidoreductase 75 kDa subunit, mit Q9UMX5 NENF Neudesin 85-94GAPYNALTGK (SEQ ID NO: 489) 6 Adapter, Scaffolding, Modulator ProteinsP55769 NHP2L1 NHP2- 114-125 QQIQSIQQSIER  3 2 6 Transcriptionlike protein 1 (SEQ ID NO: 490) factors, Regulators Q9BPW8 NIPSNAP1255-268 GWDENVYYTVPLVR (SEQ ID NO: 4 6 Uncategorized Protein NipSnap491) homolog 1 Q9Y3T9 NOC2L 591-606 VSFGVSEQQAVEAWEK (SEQ ID 2Transcription Nucleolar NO: 492) factors, complex protein Regulators2 homolog Q15233 NONO Non- 127-135 VELDNMPLR (SEQ ID NO: 493) 3Transcription POU domain- factors, containing Regulators octamer-bindingprotein Q15233 NONO Non- 257-270 FAQPGSFEYEYAMR (SEQ ID NO: 6Transcription POU domain- 494) factors, containing Regulatorsoctamer-binding protein Q15233 NONO Non- 296-304LEMEMEAAR (SEQ ID NO: 495) 6 Transcription POU domain- factors,containing Regulators octamer-binding protein Q15233 NONO Non- 154-176NLPQYVSNELLEEAFSVFGQVER 13 14 Transcription POU domain- (SEQ ID NO: 496)3 2 6 factors, containing 9 Regulators octamer-binding protein Q15233NONO Non- 177-184 AVVIVDDR (SEQ ID NO: 497) 6 Transcription POU domain-factors, containing Regulators octamer-binding protein Q15233 NONO Non-326-336 MEELHNQEVQK (SEQ ID NO: 498) 13 Transcription POU domain-factors, containing Regulators octamer-binding protein Q15233 NONO Non-435-456 FGQAATMEGIGAIGGTPPAFNR 6 Transcription POU domain-(SEQ ID NO: 499) factors, containing Regulators octamer-binding proteinP06748 NPM1  278-291 MTDQEAIQDLWQWR (SEQ ID 13 Chaperones NucleophosminNO: 500) P06748 NPM1  33-45 VDNDENEHQLSLR (SEQ ID 13 ChaperonesNucleophosmin NO: 501) P06748 NPM1  55-73 DELHIVEAEAMNYEGSPIK 13Chaperones Nucleophosmin (SEQ ID NO: 69) P06748 NPM1  81-101MSVQPTVSLGGFEITPPVVLR 13 Chaperones Nucleophosmin (SEQ ID NO: 70) Q08J23NSUN2 tRNA 603-618 LAQEGIYTLYPFINSR 3 6 Transcription (cytosine(34)-(SEQ ID NO: 502) factors, C(5))- Regulators methyltransferase Q9BV86NTMT1 N- 167-185 DNMAQEGVILDDVDSSVCR  13 Enzymes terminal Xaa-(SEQ ID NO: 503) Pro-Lys N- methyltransferase 1 Q02818 NUCB1  54-69YLQEVIDVLETDGHFR  13 14 Transcription Nucleobindin-1 (SEQ ID NO: 504)2 4 3 factors, 6 Regulators P80303 NUCB2 60-69 QVIDVLETDK 4 13 6Transcription Nucleobindin-1 (SEQ ID NO: 505) factors, Regulators Q9BQG2NUDT12 Peroxisomal 143-166 ESHPATVFILFSDLNPLVTLGGNK 15 Enzymes NADH(SEQ ID NO: 506) pyrophosphatase NUDT12 A8MXV4 NUDT19 223-252EPPPVYPDLAEVVGYQWSSPSEA 6 Enzymes Nucleoside TESFLSK (SEQ ID NO: 507)diphosphate- linked moiety X motif 19, mitochodrial O75694 NUP155952-968 HGEPEEDIVGLQAFQER  13 Channels, Nuclear pore (SEQ ID NO: 508)Transporters, complex protein Receptors Nup155 Q12769 NUP160 638-661AAEQILEDMITIDVENVMEDICSK 14 Channels, Nuclear pore (SEQ ID NO: 509)Transporters, complex protein Receptors Nup160 Q92621 NUP205 1235-1252VLVAEVNALQGMAAIGQR  14 Channels, Nuclear pore (SEQ ID NO: 510Transporters, complex protein Receptors Nup205 P35658 NUP214 770-783TTLLEGFAGVEEAR  14 Channels, Nuclear pore (SEQ ID NO: 511) Transporters,complex protein Receptors Nup214 Q8NFH4 NUP37 136-150 EGQEIASVSDDHTCR 13 9 Channels, Nucleoporin (SEQ ID NO: 512) Transporters, Nup37Receptors Q8N1F7 NUP93 Nuclear 539-545 FESTDPR  4 Channels, pore complex(SEQ ID NO: 513) Transporters, protein Nup93 Receptors P61970NUTF2 Nuclear 91-106 ADEDPIMGFHQMFLLK  14 Channels, transport factor (SEQ ID NO: 514) Transporters, 2 Receptors Q6DKJ4 NXN 384-403DYTNLPEAAPLLTILDMSAR  14 Enzymes Nucleoredoxin (SEQ ID NO: 515) P04181OAT Ornithine 33-46 TVQGPPTSDDIFER  14 13 Enzymes aminotransferase,(SEQ ID NO: 516) mitochondrial P04181 OAT Ornithine 332-351VAIAALEVLEEENLAENADK 14 13 Enzymes aminotransferase, (SEQ ID NO: 517)mitochondrial Q9NX40 OCIAD1 OCIA 34-46 VFAECNDESFWFR  13 2 Uncategorizeddomain- (SEQ ID NO: 518) containing protein 1 O60313 OPA1 Dynamin-801-818 CNEEHPAYLASDEITTVR  13 Enzymes like 120 kDa (SEQ ID NO: 519protein, mitochondrial P07237 P4HB Protein 133-162TGPAATTLPDGAAAESLVESSEVA 14 3 9 Chaperones disulfide-VIGFFK (SEQ ID NO: 520) isomerase P07237 P4HB Protein 171-195QFLQAAEAIDDIPFGITSNSDVFSK 9 Chaperones disulfide- (SEQ ID NO: 521)isomerase P07237 P4HB Protein 231-247 HNQLPLVIEFTEQTAPK  14 2 Chaperonesdisulfide- (SEQ ID NO: 522) 13 isomerase P11940 PABPC1 114-129ALYDTFSAFGNILSCK 14 Transcription Polyadenylate- (SEQ ID NO: 523)factors, binding protein Regulators 1 P11940 PABPC1 51-67SLGYAYVNFQQPADAER  14 3 Transcription Polyadenylate- (SEQ ID NO: 524)factors, binding protein Regulators 1 P11940 PABPC1 581-604ITGMLLEIDNSELLHMLESPESLR 14 Transcription Polyadenylate-(SEQ ID NO: 525) factors, binding protein Regulators 1 Q11310 PABPC451-67 SLGYAYVNFQQPADAER 14 3 Transcription Polyadenylate-(SEQ ID NO: 526) factors, binding protein Regulators 4 Q13310 PABPC4590-613 ITGMLLEIDNSELLHMLESPESLR 14 Transcription Polyadenylate-(SEQ ID NO: 527) factors, binding protein Regulators 4 Q13310 PABPC4114-129 ALYDTFSAFGNILSCK 14 Transcription Polyadenylate-(SEQ ID NO: 528) factors, binding protein Regulators 4VEMLDNLLDIEVAYSLLR 3 6 Transcription P09874 PARP1 Poly 762-779(SEQ ID NO: 529) factors, Regulators P09874 PARP1 Poly 954-1000TTPDPSANISLDGVDVPLGTGISSG 3 Transcription VNDTSLLYNEYIVYDIAQVNLKfactors, (SEQ ID NO: 530) Regulators Q16822 PCK2 245-261EIISFGSGYGGNSLLGK 14 15 Enzymes Phosphoenolypr (SEQ ID NO: 531) 13 uvatecarboxykinase P22061 PCMT1 Protein- 179-197 LILPVGPAGGNQMLEQYDK 14 3 2Enzymes L- (SEQ ID NO: 71) isoaspartate(D- aspartate) O-methyltransferase P12004 PCNA 118-138 LMDLDVEQLGIPEQEYSCVVK 14Transcription Proliferating cell (SEQ ID NO: 532) factors,nuclear antigen Regulators Q9UHG3 PCYOX1 267-280 SNLISGSVMYIEEK 14 9Enzymes Prenylcysteine (SEQ ID NO: 533) oxidase 1 Q9UHG3 PCYOX1 292-304MYEVVYQIGTETR 9 Enzymes Prenylcysteine (SEQ ID NO: 534) oxidase 1 Q9UHG3PCYOX1 152-162 MHMWVEDVLDK  4 13 Enzymes Prenylcysteine (SEQ ID NO: 535)oxidase 1 Q9UHG3 PCYOX1 37-54 IAIIGAGIGGTSAAYYLR 14 EnzymesPrenylcysteine (SEQ ID NO: 536) oxidase 1 Q53EL6 PDCD4 246-256DLPELALDTPR (SEQ ID NO: 537) 13 Transcription Programmed  factors,cell death Regulators protein 4 P11177 PDHB Pyruvate 53-68VFLLGEEVAQYDGAYK 13 14 Enzymes dehydrogenase (SEQ ID NO: 72) 3 2E1 component subunit beta, P13667 PDIA4 Protein 486-499 FAMEPEEFDSDTLR 9Enzymes disulfide- (SEQ ID NO: 538) isomerase A4 Q29RF7 PDS5A Sister638-657 SIEGTADDEEEGVSPDTAIR 13 Uncategorized chromatid (SEQ ID NO: 539)cohesion protein PDS5 homolog A Q99471 PFDN5 20-37 NQLDQEVEFLSTSIAQLK 2Chaperones Prefoldin (SEQ ID NO: 540) subunit 5 P07737 PFN1 Profilin-139-54 TFVNITPAEVGVLVGK 13 Adapter, (SEQ ID NO: 541) Scaffolding,Modulator Proteins P07737 PFN1 Profilin-1 76-89 DSLLQDGEFSMDLR  13 8Adapter, (SEQ ID NO: 542) Scaffolding, Modulator Proteins P00558 PGK1333-350 QIVWNGPVGVFEWEAFAR 3 Enzymes Phosphoglycerate (SEQ ID NO: 73)kinase 1 O00264 PGRMC1 106-119 FYGPEGPYGVFAGR 14 2 4 Channels, Membrane-(SEQ ID NO: 543) 3 13 Transporters, associated Receptors progesteronereceptor component O00264 PGRMC1 48-67 GDQPAASGDSDDDEPPPLPR 13 14Channels, Membrane- (SEQ ID NO: 544) 2 4 8 Transporters, associatedReceptors progesterone receptor component O15173 PGRMC2 136-149FYGPAGPYGIFAGR 4 Channels, Membrane- (SEQ ID NO: 545) Transporters,associated Receptors progesterone receptor component P35232PHB Prohibitin 220-239 AAELIANSLATAGDGLIELR 9 Uncategorized(SEQ ID NO: 546) P35232 PHB Prohibitin 241-253 LEAAEDIAYQLSR  14Uncategorized (SEQ ID NO: 547) P35232 PHB Prohibitin 42501VFESIGK (SEQ ID NO: 548) 13 Uncategorized Q99623 PHB2 38-48ESVFTVEGGHR (SEQ ID NO: 549) 2 6 Channels, Prohibitin-2 Transporters,Receptors Q99623 PHB2 55-71 IGGVQQDTILAEGLHFR 3 4 2 Channels,Prohibitin-2 (SEQ ID NO: 550) 6 Transporters, Receptors Q99623 PHB2225-236 IVQAEGEAEAAK 6 Channels, Prohibitin-2 (SEQ ID NO: 551)Transporters, Receptors O43175 PHGDH D-3- 295-308 CGEEIAVQFVDMVK 13Enzymes phosphoglycerate (SEQ ID NO: 552) dehydrogenase P48739 PITPNB32-44 NETGGGEGIEVLK 14 3 Adapter, Phosphatidylino (SEQ ID NO: 553)Scaffolding, sitol transfer Modulator protein beta Proteins isoformQ5JRX3 PITRM1 364-385 ALIESGLGTDFSPDVGYNGYTR 14 2 Enzymes PresequenceTQNGR (SEQ ID NO: 554) 13 8 6 protease, mitochondrial P14618PKM Pyruvate 174-186 IYVDDGLISLQVK 2 9 Enzymes kinase isozymes(SEQ ID NO: 74) M1/M2 P14618 PKM Pyruvate 401-422 LAPITSDPTEATAVGAVEASFK2 9 Enzymes kinase isozymes (SEQ ID NO: 75) M1/M2 Q8IV08 PLD3 425-453ATYIGTSNWSGNYFTETAGTSLLV 3 6 9 Enzymes PhospholipaseTQNGR (SEQ ID NO: 555) D3 P13797 PLS3 Plastin-3 72-85 ISFDEFVYIFQEVK 14Uncategorized (SEQ ID NO: 556) Q10713 PMPCA 443-451PVIFEDVGR (SEQ ID NO: 557) 14 8 6 Enzymes Mitochondrial- processing peptidase subunit alpha O75439 PMPCB 406-424 TNMLLQLDGSTPICEDIGR 13Enzymes Mitochondrial- (SEQ ID NO: 558) processing  peptidasesubunit beta Q9Y2S7 POLDIP2 166-199 ALYAIPGLDYVSHEDILPYTSTDQ 6Uncategorized Polymerase VPIQHELFER (SEQ ID NO: 559) delta-interactingprotein 2 O00411 POLRMT DNA- 482-502 MLLQVLQALPAQGESFTTLAR 14 3 2Enzymes directed RNA (SEQ ID NO: 560) 6 polymerase, mitochondrial P16435POR NADPH-- 369-382 TALTYYLDITNPPR 13 14 Enzymes cytochrome(SEQ ID NO: 76) P450 reductase P62136 PPP1CA 133-141 IYGFYDECK 2 EnzymesSerine/threonine- (SEQ ID NO: 77) protein phosphate PP1-alpha cat P62140PPP1CB 132-140 IYGFYDECK 2 Enzymes Serine/threonine- (SEQ ID NO: 78)protein phosphate PP1-alpha cat P62140 PPP1CB 43-59 IEFLSQPILLELEAPLK 14Enzymes Serine/threonine- (SEQ ID NO: 79) protein phosphatePP1-alpha cat P36873 PPP1CC 44-60 EIFLSQPILLELEAPLK 14 EnzymesSerine/threonine- (SEQ ID NO: 79) protein phosphate PP1-gamma cat P36873PPP1CC 133-141 IYGFYDECK 2 Enzymes Serine/threonine- (SEQ ID NO: 78)protein phosphate PP1-gamma cat P50897 PPT1 Palmitoyl- 75-101TLMEDVENSFFLNVNSQVTTVCQ 13 14 Enzymes protein ALKA 15 4 2 thioesterase 1(SEQ ID NO: 80) 9 8 P32119 PRDX2 120-127 TDEGIAYR 13 EnzymesPeroxiredoxin-2 (SEQ ID NO: 81) P78527 PRKDC DNA- 3030-3046IWSEPFYQETLPYMIR 14 Enzymes dependent (SEQ ID NO: 561) protein kinasecatalytic subunit P78527 PRKDC DNA- 758-782 LGLSYTPLAEVGLNALEEWSIYID 14Enzymes dependent R (SEQ ID NO: 562) protein kinase catalytic subunitQ99873 PRMT1 Protein 380-391 DVDFMYVELIQR 13 Enzymes argine N-(SEQ ID NO: 563) methyltransferase 1 Q9UMS4 PRPF19 Pre- 186-196ATLYVTAIEDR (SEQ ID NO: 564) 14 Enzymes mRNA- processing  factor 19P07602 PSAP  77-93 ALQDEWDAVMLHSFTLR 4 Adapter, Proactivator(SEQ ID NO: 565) Scaffolding, polypeptide Modulator P07602 PSAP Proteins Proactivator 108-122 EIVDSYLPVILDIIK 13 14 Adapter, polypeptide(SEQ ID NO: 566) 3 2 4 Scaffolding, 15 6 9 Modulator 8 Proteins P07602PSAP  263-275 EICALVGFCDEVK 14 Adapter, Proactivator (SEQ ID NO: 567)Scaffolding, polypeptide Modulator Proteins P07602 PSAP  311-323SDVYCEVCEFLVK 13 4 9 Adapter, Proactivator (SEQ ID NO: 568) 8Scaffolding, polypeptide Modulator Proteins P07602 PSAP  430-438QEILAALEK (SEQ ID NO: 569) 2 6 Adapter, Proactivator Scaffolding,polypeptide Modulator Proteins P07602 PSAP  439-449GCSFLPDPYQK (SEQ ID NO: 570) 14 9 Adapter, Proactivator Scaffolding,polypeptide Modulator Proteins P07602 PSAP  450-478QCDQFVAEYEPVLIEILVEVMDPS 14 4 9 Adapter, ProactivatorFVCLK (SEQ ID NO: 571) Scaffolding, polypeptide Modulator ProteinsP07602 PSAP  68-78 DVVTAAGDMLK 14 4 9 Adapter, Proactivator(SEQ ID NO: 572) Scaffolding, polypeptide Modulator Proteins P25787PSMA2 144-159 PYLFQSDPSGAYFAWK 2 Enzymes Proteasome (SEQ ID NO: 573)subunit alpha type-2 P25787 PSMA2 19-39 LVQIEYALAAVAGGAPSVGIK 3 EnzymesProteasome (SEQ ID NO: 574) subunit alpha type-2 P25789 PSMA4 68-91LNEDMACSVAGITSDANVLTNEL 13 14 Enzymes Proteasome R (SEQ ID NO: 575)3 6 8 subunit alpha type-4 P20618 PSMB1 129-146 FFPYYVYNIIGGLDEEGK 13 14Enzymes Proteasome (SEQ ID NO: 576) 2 15 subunit beta type-1 P49721PSMB2 96-126 TPYHVNLLLAGYDEHEGPALYY 2 6 Enzymes ProteasomeMDYLAALAK (SEQ ID NO: 577) subunit beta type-2 P49721 PSMB2 42-62ILLLCVGEAGDTVQFAEYIQ 6 Enzymes Proteasome (SEQ ID NO: 578) subunit betatype-2 P49720 PSMB3 100-115 FGPYYTEPVIAGLDPK 13 14 Enzymes Proteasome(SEQ ID NO: 579) 15 3 6 subunit beta type-3 P28070 PSMB4 61-80FEGGVVIAADMLGSYGSLAR 6 Enzymes Proteasome (SEQ ID NO: 82) subunit betatype-4 P28074 PSMB5 141-150 LLANMVYQYK 4 3 6 Enzymes Proteasome(SEQ ID NO: 83) subunit beta type-5 P28074 PSMA5 226-239 DAYSGGAVNLYHVR6 Enzymes Proteasome (SEQ ID NO: 84) subunit beta type-5 P28072 PSMB680-118 SGSAADTQAVADAVTYQLGFHSI 14 3 6 Enzymes ProteasomeELNEPPLVHTAASLFK subunit beta (SEQ ID NO: 85) type-6 O00231 PSMD11 26S164-175 ALLVEVQLLESK 2 Uncategorized proteasome non- (SEQ ID NO: 580)ATPase regulatory subunit 11 O00231 PSMD11 26S 227-246TAYSYFYEAFEGYDSIDSPK 2 4 Uncategorized proteasome non- (SEQ ID NO: 581)ATPase regulatory subunit 11 O00231 PSMD11 26S 298-304SLADFEX (SEQ ID NO: 582) 4 Uncategorized proteasome non- ATPaseregulatory subunit 11 242-256 HDADGQATLLNLLLR 14 4 O43242 PSMD3 26S(SEQ ID NO: 583) Uncategorized proteasome non- ATPase regulatorysubunit 3 O43242 PSMD3 26S 426-440 LQLDSPEDAEFIVAK 14 Uncategorizedproteasome non- (SEQ ID NO: 584) ATPase regulatory subunit 3 Q9UL46PSME2 132-145 IEDGNDFGVAIQEK 6 Uncategorized Proteasome (SEQ ID NO: 585)activator complex subunit 2 P61289 PSME3 147-166 IEDGNNFGVSIQEETVAELR14 4 Uncategorized Proteasome (SEQ ID NO: 586) 13 8 activatorcomplex subunit 3 P61289 PSME3 167-181 TVESEAASYLDQISR 13 4 8Uncategorized Proteasome (SEQ ID NO: 587) activator complex subunit 3P61289 PSME3 22-36 ITSEAEDLVANFFPK 4 Uncategorized Proteasome(SEQ ID NO: 588) activator complex subunit 3 Q8WXF1 PSPC1 229-247PVIVEPMEQFDDEDGLPEK 14 6 Transcription Paraspeckle (SEQ ID NO: 589)factors, component 1 Regulators P26599 PTBP1 219-238 NNQFQALLQYADPVSAQHA14 Transcription Polypyrimidine (SEQ ID NO: 590) factors, tract-binding Regulators protein 1 Q96EY7 PTCD3 119-126 FIINSYPK (SEQ ID NO: 591) 2Transcription Pentatricopeptide factors, repeat- Regulators containingprotein 3, mit Q8N8N7 PTGR2 93-106 GDFVTSFYWPWQTK 14 EnzymesProstaglandin (SEQ ID NO: 592) reductase 2 Q8N8N7 PTGR2 262-278DVPYPPPLSPAIEAIQK 14 3 2 Enzymes Prostaglandin (SEQ ID NO: 593)reductase 2 Q9P035 PTPLAD1 3- 133-146 LESEGSPETLTNLR 13 Enzymeshydroxyacyl- (SEQ ID NO: 594) CoA dehydratase 3 Q9UHX1 PUF60 Poly(U)-474-489 DIDDDLEGEVTEECGK 13 15 Transcription binding-splicing(SEQ ID NO: 595) 14 4 8 factors, factor PUF60 Regulators Q5XLP0QIL1 Protein 15-36 GSVAGGAVYLVYDQELLGPSDK 14 Uncategorized QIL1(SEQ ID NO: 596) Q96PU8 QKI Protein  192-205 MQLMELAILNGTYR 2 Channels,quaking (SEQ ID NO: 597) Transporters, Receptors P51149 RAB7A Ras-104-113 DEFLIQASPR 14 Adapter, related protein (SEQ ID NO: 86)Scaffolding, Rab-7a Modulator Proteins Q7Z6M1 RABEPK Rab9 87-100YEHASFIPSCTPDR 14 Uncategorized effector protein (SEQ ID NO: 598)with kelch motifs P11233 RALA Ras- 28-47 SALTLQFMYDEFVEDYEPTK 9Transcription related protein (SEQ ID NO: 599) factors, Ral-A RegulatorsP54136 RARS Arginine-- 528-540 GNTAAYLLYAFTR 14 Enzymes tRNA ligase,(SEQ ID NO: 600) cytoplasmic Q96PK6 RBM14 RNA- 224-238 ASYVAPTAQPATYR 6Transcription binding protein (SEQ ID NO: 601) factors, 14 RegulatorsQ96PK6 RBM14 RNA- 65-72 ALVVEMSR (SEQ ID NO: 602) 6 Transcriptionbinding protein factors, 14 Regulators P98179 RMB3 Putative 8-39LFVGGLNFNTDEQALEDHFSSFGP 13 3 2 Transcription RNA-bindingISEVVVVK (SEQ ID NO: 603) 9 factors, protein 3 Regulators P38159RMBX RNA- 126-144 GGHMDDGGYSMNFNMSSSR 6 Transcription binding motif(SEQ ID NO: 604) factors, protein, X Regulators chromosome P38159RMBX RNA- 23-30 ALEAVFGK (SEQ ID NO: 605) 3 13 6 Transcriptionbinding motif factors, protein, X Regulators chromosome P38159 RMBX RNA-245-252 DYGHSSSR (SEQ ID NO: 606) 3 Transcription binding motif factors,protein, X Regulators chromosome P38159 RMBX RNA- 283-292DSYESYGNSR (SEQ ID NO: 607) 6 Transcription binding motif factors,protein, X Regulators chromosome P38159 RMBX RNA- 299-309GPPPSYGGSSR (SEQ ID NO: 608 6 Transcription binding motif factors,protein, X Regulators chromosome P38159 RMBX RNA- 332-339SDLYSSGR (SEQ ID NO: 609) 6 Transcription binding motif factors,protein, X Regulators chromosome P38159 RMBX RNA- 50-63 GFAFVTFESPADAK 6Transcription binding motif (SEQ ID NO: 610) factors, protein, XRegulators chromosome Q96E39 RBMXL1 RNA 299-309GPPPSYGGSSR (SEQ ID NO: 611) 6 Transcription binding motif factors,protein, X- Regulators linked-like-1 Q96E39 RBMXL1 RNA 50-63GFAFVTFESPADAK 6 Transcription binding motif (SEQ ID NO: 612) factors,protein, X- Regulators linked-like-1 Q96E39 RBMXL1 RNA 245-252DYGHSSSR (SEQ ID NO: 613) 3 Transcription binding motif factors,protein, X- Regulators linked-like-1 Q96E39 RBMXL1 RNA 283-292DSYESYGNSR (SEQ ID NO: 614) 6 Transcription binding motif factors,protein, X- Regulators linked-like-1 Q96E39 RBMXL1 RNA 126-144GGHMDDGGYSMNFNMSSR 6 Transcription binding motif (SEQ ID NO: 615)factors, protein, X- Regulators linked-like-1 Q15293 RCN1 91-105IDNDGDGFVTTEELK 13 Uncategorized Reticulocalbin-1 (SEQ ID NO: 616)Q14257 RCN2 283-305 LSEEEILENPDLFLTSEATDYGR 14 3 UncategorizedReticulocalbin-2 (SEQ ID NO: 617) 15 6 9 8 Q14257 RCN2 130-148VIDFDENTALDDAEEESFR 13 9 Uncategorized Reticulocalbin-2 (SEQ ID NO: 618)6 Q14257 RCN2 217-232 WDPTANEDPEWILVE 14 4 6 UncategorizedReticulocalbin-2 (SEQ ID NO: 619) Q14257 RCN2 96-103HYAMQEAK (SEQ ID NO: 620) 6 Uncategorized Reticulocalbin-2 Q14257 RCN2161-200 ANQDSGPGLSLEEFIAFEHPEEVD 9 Uncategorized Reticulocalbin-2YMTEFVIQEALEEHDK (SEQ ID NO: 621) P35250 RBC2 211-230VPYTDDGLEAIIFTAQGDMR 13 Transcription Replication (SEQ ID NO: 622)factors, factor C subunit  Regulators 2 P62888 RPL30 60S 58-68SEIEYYAMLAK (SEQ ID NO: 623) 13 Uncategorized ribosomal protein L30P62917 RPL8 60S 129-144 ASGNYATVISHNPETK 2 Transcription ribosomal(SEQ ID NO: 624) factors, protein L8 Regulators P05387 RPLP2 60S 50-61NIEDVIAQGIGK  14 Uncategorized acidic ribosomal (SEQ ID NO: 625)protein P2 P04843 RPN1 Dolichyl- 152-169 QFVVFEGNHYFYSPYPTK 6 Enzymesdiphosphooligos (SEQ ID NO: 626) accharide-- protein glycosyltransferase subunit 1 P04843 RPN1 Dolichyl- 328-352 THYIVGYNLPSYEYLYNLGDQYA 6Enzymes diphosphooligos LK (SEQ ID NO: 627) accharide-- proteinglycosyltransfer ase subunit 1 P04843 RPN1 Dolichyl- 525-536ALTSEIALLQSR  13 6 Enzymes diphosphooligos (SEQ ID NO: 628) accharide--protein glycosyltransfer ase subunit 1 P04844 RPN2 Dolichyl- 155-178EETVLATVQALQTASHLSQQADL 6 Enzymes diphosphooligos (SEQ ID NO: 629)accharide-- protein glycosyltransfer ase subunit 2 P04844 RPN2 Dolichyl-179-190 SIVEEIEDLVAR  14 3 Enzymes diphosphooligos (SEQ ID NO: 630)13 6 9 accharide-- protein glycosyltransfer ase subunit 2 P04844RPN2 Dolichyl- 443-456 TGQEVVFVAEPDNK 9 Enzymes diphosphooligos(SEQ ID NO: 631) accharide-- protein glycosyltransfer ase subunit 2P46783 RPS10 40S 81-95 DYLHLPPEIVPATR 3 13 Uncategorized ribosomal(SEQ ID NO: 632) protein S10 P23396 RPS3 40S 152-173FVDGLMIHSGDPVNYYVDTAVR 6 Transcription ribosomal (SEQ ID NO: 633)factors, protein S3 Regulators P23396 RPS3 40S 28-40 ELAEDGYSGVEVR 13 6Transcription ribosomal (SEQ ID NO: 634) factors, protein S3 RegulatorsP23396 RPS3 40S 46-54 TEIIILATR (SEQ ID NO: 635) 6 Transcriptionribosomal factors, protein S3 Regulators P23396 RPS3 40S 77-90FGFPEGSVELYAEK 2 6 Transcription ribosomal (SEQ ID NO: 636) factors,protein S3 Regulators P62241 RPS8 40S 158-170 ISSLLEEQFQGK 13Uncategorized ribosomal (SEQ ID NO: 637) protein S8 Q9NQC3 RTN41075-1090 AYLESEVAISEELVQK 13 14 Uncategorized Reticulon-4(SEQ ID NO: 638) Q9Y265 RUVBL1 RuvB- 318-333 ALESSIAPIVIFASNR 2 Enzymeslike 1 (SEQ ID NO: 639) Q9Y265 RUVBL1 RuvB- 91-107 VPFCPMVGSEVYSTEIK 2Enzymes like 1 (SEQ ID NO: 640) Q9Y230 RUVBL2 RuvB- 315-330ALESDMAPVLIMATNR 14 Transcription like 2 (SEQ ID NO: 87) factors,Regulators Q9Y512 SAMM50 128-148 LTGSYNTMVGNNEGSMVLGLK 14 4Uncategorized Sorting and (SEQ ID NO: 641) assembly machinerycomponent 50 homolo Q8NBX0 SCCPDH 145-167 GVYIIGSSGFDSIPADLGVIYTR 14Enzymes Saccharopine (SEQ ID NO: 642) dehydrogenase- like oxidoreductaseQ9HB40 SCPEP1 256-275 AEMIIEQNTDGVNFYNILTK 13 14 Enzymes Retinoid-(SEQ ID NO: 643) 15 3 2 inducible serine 4 6 9 carboxypeptidase 8 Q01105SET Protein 91-122 IPNFWVTTFVNHPQVSALLGEEDE 3 Chaperones SETEALHYLTR (SEQ ID NO: 644) P23246 SFPQ Splicing 377-399NLSPYVSNELLEEAFSQFGPIER 13 14 Transcription factor, proline-(SEQ ID NO: 645) 3 2 4 factors, and glutamine- 9 Regulators rich P23246SFPQ Splicing 444-462 PVIVEPLEQLDDEDGLPEK 14 4 2 Transcriptionfactor, proline- (SEQ ID NO: 646) factors, and glutamine- Regulatorsrich Q9H9B4 SFXN1 36-48 NILLTNEQLESAR 14 Channels Sideroflexin-1(SEQ ID NO: 647) Transporters, Receptors Q9H9B4 SFXN1 137-170SGDAPLTVNELGTAYVSATTGAV 14 Channels Sideroflexin-1ATALGLNALTK (SEQ ID NO: 648) Transporters, Receptors Q9H9B4 SFXN1 56-70QGIVPPGLTENELWR 14 Channels Sideroflexin-1 (SEQ ID NO: 649)Transporters, Receptors Q9H9B4 SFXN1 93-112 MSAQVPMNMTITGCMMTFYR 6Channels Sideroflexin-1 (SEQ ID NO: 650) Transporters, Receptors Q9H9B4SFXN1 234-253 ILMAAPGMAIPPFIMNTLEK 6 Channels Sideroflexin-1(SEQ ID NO: 651) Transporters, Receptors Q6P4A7 SFXN4 43-66FLQWTELLDPTNVFISVESIENSR 14 2 Channels Sideroflexin-4 (SEQ ID NO: 652)Transporters, Receptors O95470 SGPL1 42699 AFEPYLEILEVYSTK 14 EnzymesSphingosine-1- (SEQ ID NO: 653) phophate lyase 1 Q9Y371 SH3GLB1 22-29AVQFTEEK (SEQ ID NO: 654) 4 8 Adapter, Endophilin-B1 Scaffolding,Modulator Proteins P34897 SHMT2 Serine 105-121 YYGGAEVVDEIELLCQR 13 14Enzymes hydroxymethyltr (SEQ ID NO: 655) 15 3 2 ansferase, 8mitochondrial Q9UBX3 SLC25A10 171-186 GALVTVGQLSCYDQAK 14 ChannelsMitochondrial (SEQ ID NO: 656) Transporters, dicarboxylate Receptorscarrier O75746 SCLC25A12 260-283 YGQVTPLEIDILYQLADLYNASGR 14 4 ChannelsCalcium-binding (SEQ ID NO: 657) Transporters, mitochondrial Receptorscarrier protein Aral O75746 SCLC25A12 641-652 LATATFAGIENK  14 4Channels Calcium-binding (SEQ ID NO: 658) Transporters, mitochondrialReceptors carrier protein Aral Q9UJS0 SCLC25A13 293-310IAPLEEGTLPFNLAEAQR 4 6 Channels Calcium-binding (SEQ ID NO: 659)Transporters, mitochondrial Receptors carrier protein Aral Q9UJS0SCLC25A13 261-282 FGQVTPMEVDILFQLADLYEPR 14 15 Channels Calcium-binding(SEQ ID NO: 660) 3 4 2 Transporters, mitochondrial 6 Receptorscarrier protein Aral Q9UJS0 SCLC25A13 642-653 LAVATFAGIENK  14 4 3Channels Calcium-binding (SEQ ID NO: 661) 15 6 8 Transporters,mitochondrial Receptors carrier protein Aral Q6NUK1 SCLC25A24 454-469VLPAVGISYVVYENMK 2 Channels Calcium-binding (SEQ ID NO: 662)Transporters, mitochondrial Receptors carrier protein SCaM Q00325SLC25A3 146-161 VLYSNMLGEENTYLWR 4 Channels Phophate (SEQ ID NO: 663)Transporters, carrier protein, Receptors mitochondrial Q00325 SLC25A3162-187 TSLYLAASASAEFFADIALAPMEA 4 Channels Phophate AK (SEQ ID NO: 664)Transporters, carrier protein, Receptors mitochondrial Q9H2D1 SLC25A32118-145 LEATEYLVSAAEAGAMTLCITNPL 14 Channels MitochondrialWVTK (SEQ ID NO: 665) Transporters, folate Receptors transporter/carrierP12235 SLC25A4 189-199 AAYFGVYDTAK (SEQ ID NO: 666) 14 2 8 ChannelsADP/ATP 4 Transporters, translocase 1 Receptors Q8TBP6 SLC25A40 136-152LGENETCIPIVAGIVAR 14 Channels Solute carrier (SEQ ID NO: 667)Transporters, family 25 Receptors member 40 P05141 SLC25A5 42697DFLAGGVAAAISK 14 2 4 Channels ADP/ATP (SEQ ID NO: 668) Transporters,translocase 2 Receptors P05141 SLC25A5 189-199AAYFGIYDTAK (SEQ ID NO: 669) 14 2 4 Channels ADP/ATP 3 9 8 Transporters,translocase 2 Receptors P12236 SLC25A6 42697 DFLAGGIAAAISK 14 4 2Channels ADP/ATP (SEQ ID NO: 670) 13 Transporters, translocase 3Receptors P12236 SLC25A6 189-199 AAYFGVYDTAK (SEQ ID NO: 671) 14 2 8Channels ADP/ATP 4 Transporters, translocase 3 Receptors Q8IXU6SLC35F2 Solute 188-221 EDNSGSDVLIGDILVLLGASLYAIS 9 Channelscarrier family 35 NVCEEYIVK (SEQ ID NO: 672) Transporters, member F2Receptors Q9H2G2 SLK STE20-like 27-47 DLNPEDFWEIIGELGDGAFGK 6 Enzymesserine/threonine- (SEQ ID NO: 673) protein kinase Q92922 SMARCC1 894-905SLVALLVETQMK 13 Transcription SWI/SNF (SEQ ID NO: 674) factors,complex subunit Regulators SMARCC1 Q14683 SMC1A 1070-1086FNACFESVATNIDEIYK 8 Adapter, Structureal (SEQ ID NO: 675) Scaffolding,maintenance of Modulator chromosomes Proteins protein 1A Q9H7B4SMYD3 SET 255-265 DQYCFECDCFR 9 Enzymes and MYND (SEQ ID NO: 88) domain-containing protein 3 Q96DI7 SNRNP40 U5 233-260 GHADSVTGLSLSSEGSYLLSNAM13 Uncategorized small nuclear DNTVR (SEQ ID NO: 676) ribonucleoprotein40 kDa protein P62314 SNRNP40 U5 67-86 YFILPDSLPLDTLLVDVEPK 13Uncategorized small nuclear (SEQ ID NO: 677) ribonucleoprotein Sm D1Q13813 SPTAN1 2354-2382 SLGYDLPMVEEGEPDPEFEAILDT 13 14 Adapter,Spectrin alpha VDPNR (SEQ ID NO: 678) Scaffolding, chain, non- Modulatorerythrocytic 1 Proteins Q01082 SPTAN1 1706-1717 EVDDLEQWIAER 13 Adapter,Spectrin beta (SEQ ID NO: 679) Scaffolding, chain, non- Modulatorerythrocytic 1 Proteins Q9UHB9 SRP68 Signal 312-333IFLLGLADNEAAIVQAESEETK 14 13 Transcription recognition (SEQ ID NO: 680)factors, particle 68 kDa Regulators protein Q04837 SSBP1 Single- 67-81SGDSEVYQLGDVSQK 13 8 Transcription stranded DNA- (SEQ ID NO: 681)factors, binding protein, Regulators mitochondrial Q8N3U4 STAG2 Cohesin273-290 ELQENQDEIENMMNAIFK 13 Uncategorized subunit SA-2(SEQ ID NO: 682) P31948 STIP1 Stress- 416-429 DCEECIQLEPTFIK 14Uncategorized induced- (SEQ ID NO: 683) phosphoprotein 1 Q9UJZ1 STOML258-72 ILEPGLNILIPVLDR 6 Adapter, Stomatin-like (SEQ ID NO: 684)Scaffolding, protein 2 Modulator Proteins Q9UJZ1 STOML2 35-51NTVVLFVPQQEAWVVER 6 Adapter, Stomatin-like (SEQ ID NO: 685) Scaffolding,protein 2 Modulator Proteins Q9UJZ1 STOML2 115-135 ASYGVEDPEYAVTQLAQTTMR13 8 Adapter, Stomatin-like (SEQ ID NO: 686) Scaffolding, protein 2Modulator Proteins P46977 STT3A 330-340 FYSLLDPSYAK 14 Enzymes Dolichyl-(SEQ ID NO: 687) diphosphooligos accharide-- protein glycosy P46977STT3A 59-67 FLAEEGFYK (SEQ ID NO: 688) 6 Enzymes Dolichyl-diphosphooligos accharide-- protein glycosy P46977 STT3A 672-690DFELDVLEEAYTTEHWLVR 6 Enzymes Dolichyl- (SEQ ID NO: 689) diphosphooligosaccharide-- protein glycosy P46977 STT3A 572-595ELDVSYVLVIFGGLTGYSSDDINK 9 Enzymes Dolichyl- (SEQ ID NO: 690)diphosphooligos accharide-- protein glycosy Q8TCJ2 STT3B 692-703ESDYFTPQGEFR  14 Enzymes Dolichyl- (SEQ ID NO: 691) diphosphooligosaccharide-- protein glycosy Q8TCJ2 STT3B 651-674TLDVDYVLVIFGGVIGYSGDDINK 9 Enzymes Dolichyl- (SEQ ID NO: 692)diphosphooligos accharide-- protein glycosy Q96I99 SUCLG2 151-160ETYLAILMDR (SEQ ID NO: 693) 3 Enzymes Succinyl-CoA ligase O15260SURF4 Surfeit 31-43 LCLISTFLEDGIR  13 14 Uncategorized locus protein 4(SEQ ID NO: 694) O60506 SYNCRIP 334-356 NLANTVTEEILEK 9 6 TranscriptionHeterogeneous (SEQ ID NO: 695) factors, nuclear Regulatorsribonucleoprotein Q Q92804 TAF15 TATA- 284-297 GEATVSFDDPPSAK 2Transcription binding protein- (SEQ ID NO: 696) factors,associated factor Regulators 2N Q92804 TAF15 TATA- 423-431SGGGYGGDR (SEQ ID NO: 697) 6 Transcription binding protein- factors,associated factor Regulators 2N Q12788 TBL3 755-766 AALEALLPYTER  13 8Uncategorized Transducin beta- (SEQ ID NO: 698) like protein 3 P52888THOP1 Thimet 67-79 ALADVEVTYTVQR 14 8 Enzymes oligopeptidase(SEQ ID NO: 699) P52888 THOP1 Thimet 105-115LSEFDVEMSMR (SEQ ID NO: 700) 14 Enzymes oligopeptidase P52888THOP1 Thimet 499-520 DFVEAPSQMLENWVWEQEPLLR 14 Enzymes oligopeptidase(SEQ ID NO: 701) P62072 TIMM10 42545 AQQLAAELEVEMMADMYNR 13 14Chaperones Mitochondrial (SEQ ID NO: 702) 9 8 import inner membranetranslocase su Q99595 TIMM17A 13-35 IVDDCGGAFTMGTIGGGIFQAIK 14 15Channels Mitochondrial (SEQ ID NO: 703) 2 4 8 Transporters, import innerReceptors membrane translocase su O60830 TIMM17B 13-35IVDDCGGAFTMGVIGGGVFQAIK 14 15 Channels Mitochondrial (SEQ ID NO: 704)2 4 3 Transporters, import inner 13 6 9 Receptors membranetranslocase su O43615 TIMM44 428-439 DQDELNPYAAWR 13  ChannelsMitochondrial (SEQ ID NO: 705) Transporters, import inner Receptorsmembrane translocase su P49755 TMED10 154-169 LEDLSESIVNDFAYMK 14 3 9Channels Transmembrane (SEQ ID NO: 706) Transporters, emp24 domain-Receptors containg protein 10 Q9BVK6 TMED9 49-65 CFIEEIPDETMVIGNYR 9Channels Transmembrane (SEQ ID NO: 707) Transporters, emp24 domain-Receptors containg protein 9 Q9H061 TMEM126A 85-105CFVSFPLNTGDLDCETCRITR 14 Uncategorized Transmembrane (SEQ ID NO: 708)protein 126A P42166 TMPO Lamina- 621-637 TYDAASYICEAAFDEVK 4Transcription associated (SEQ ID NO: 709) factors, polypeptide 2, Regulators isoform alpha Q92973 TNPO1 273-298 TQDQDENVALEACEFWLTLAEQP 9Channels Transportin-1 ICK (SEQ ID NO: 710) Transporters, ReceptorsQ92973 TNPO1 45-64 LEQLNQYPDFNNYLIFVLTK 13 14 Channels Transportin-1(SEQ ID NO: 711) 2 Transporters, Receptors Q9NS69 TOMM22 106-117LQMEQQQQLQQR 14 Channels Mitochondrial (SEQ ID NO: 712) Transporters,import receptor Receptors subunit TOM22 homolog Q9NS69 TOMM22 61-76SAAGATFDLSLFVAQK 14 4 2 Channels Mitochondrial (SEQ ID NO: 713) 13Transporters, import receptor Receptors subunit TOM22 homolog O96008TOMM40 278-293 ASDQLQVGVEFEASTR 14 Channels Mitochondrial(SEQ ID NO: 714) Transporters, import receptor Receptors subunit TOM40homolog O94826 TOMM70A 475-494 CAEGYALYAQALTDQQQFGK 14 UncategorizedMitochondrial (SEQ ID NO: 715) import receptor subunit TOM70 P67936 TPM4170-177 SLEAASEK (SEQ ID NO: 716) 13 3 Adapter, Tropomyosin Scaffolding,alpha-4-chain Modulator Proteins O14773 TPP1 521-558GCHESCLDEEVEGQGFCSGPGWD 13 14 Enzymes Tripeptidyl- PVTGWGTPNFPALLK15 4 9 peptidase 1 (SEQ ID NO: 89) Q9H4I3 TRABD TraB 235-253DLLEQMMAEMIGEFPDLHR 14 Uncategorized domain- (SEQ ID NO: 717) containingprotein Q12931 TRAP1 Heat 603-619 LDTHPAMVTVLEMGAAR 13 Chaperonesshock protein 75 (SEQ ID NO: 718) kDa, mitochondrial Q15631 TSN Translin205-215 VEEVVYDLSIR (SEQ ID NO: 719) 2 Transcription factors, RegulatorsQ6DKK2 TTC19 134-149 AITYTYDLMANLAFIR 6 Adapter, Tetratricopeptide(SEQ ID NO: 720) Scaffolding, repeat protein Modulator 19, Proteinsmitochondrial Q14166 TTLL12 254-287 CMLLPWAPTDMLDLSSCTPEPPA 4 EnzymesTubulin-- EHYQAILEENK (SEQ ID NO: 721) tyrosine ligase- like protein 12Q71U36 TUBA1A 353-370 VGINYQPPTVVPGGDLAK 4 Adapter, Tubulin alpha-(SEQ ID NO: 722) Scaffolding, 1A chain Modulator Proteins Q71U36 TUBA1A244-264 FDGALNVDLTEFQTNLVPYPR 13 3 2 Adapter, Tubulin alpha-(SEQ ID NO: 723) 4 Scaffolding, 1A chain Modulator Proteins Q71U36TUBA1A 281-304 AYHEQLSVAEITNACFEPANQMV 4 3 13 Adapter, Tubulin alpha-K (SEQ ID NO: 724) Scaffolding, 1A chain Modulator Proteins Q71U36TUBA1A 374-390 AVCMLSNTTAIAEAWAR 4 Adapter, Tubulin alpha-(SEQ ID NO: 725) Scaffolding, 1A chain Modulator Proteins Q71U36 TUBA1A65-79 AVFVDLEPTVIDEVR 13 4 3 Adapter, Tubulin alpha- (SEQ ID NO: 726) 2Scaffolding, 1A chain Modulator Proteins Q71U36 TUBA1A 403-422AFVHWYVGEGMEEGEFSEAR 4 Adapter, Tubulin alpha- (SEQ ID NO: 727)Scaffolding, 1A chain Modulator Proteins Q71U36 TUBA1A 41-60TIGGGDDSFNTFFSETGAGK 13 Adapter, Tubulin alpha- (SEQ ID NO: 728)Scaffolding, 1A chain Modulator Proteins Q13748 TUBA3D 244-264FDGALNVDLTEFQTNLVPYPR 14 13 Adapter, Tubulin alpha- (SEQ ID NO: 729) 9 4Scaffolding, 3C/D chain Modulator Proteins Q13748 TUBA3D 281-304AYHEQLSVAEITNACFEPANQMV 14 13 Adapter, Tubulin alpha- K (SEQ ID NO: 730)4 Scaffolding, 3C/D chain Modulator Proteins Q13748 TUBA3D 41-60TIGGGDDSFNTFFSETGAGK 13 9 Adapter, Tubulin alpha- (SEQ ID NO: 731)Scaffolding, 3C/D chain Modulator Proteins P68366 TUBA4A 244-264FDGALNVDLTEFQTNLVPYPR 3 2 13 Adapter, Tubulin alpha- (SEQ ID NO: 732)9 4 Scaffolding, 4A chain Modulator Proteins P68366 TUBA4A 281-304AYHEQLSVAEITNACFEPANQMV 3 13 4 Adapter, Tubulin alpha-K (SEQ ID NO: 733) Scaffolding, 4A chain Modulator Proteins P68366TUBA4A 340-352 SIQFVDWCPTGFK 13 Adapter, Tubulin alpha- (SEQ ID NO: 734)Scaffolding, 4A chain Modulator Proteins Q9NY65 TUBA8 Tubulin 244-264FDGALNVDLTEFQTNLVPYPR 3 2 13 Adapter, alpha-8 chain (SEQ ID NO: 735) 9 4Scaffolding, Modulator Proteins P07437 TUBB Tubulin 104-121GHYTEGAELVDSVLDVVR 13 9 Adapter, beta chain (SEQ ID NO: 736) 6Scaffolding, Modulator Proteins P07437 TUBB Tubulin 175-213VSDTVVEPYNATLSVHQLVENTD 6 Adapter, beta chain ETYCIDNEALYDICFRScaffolding, (SEQ ID NO: 737) Modulator Proteins P07437 TUBB Tubulin20-46 FWEVISDEHGIDPTGTYHGDSDLQ 6 Adapter, beta chainLDR (SEQ ID NO: 738) Scaffolding, Modulator Proteins P07437 TUBB Tubulin217-241 LTTPTYGDLNHLVSATMSGVTTC 3 13 6 Adapter, beta chainLR (SEQ ID NO: 739) Scaffolding, Modulator Proteins P07437 TUBB Tubulin283-297 ALTVPELTQQVFDAK 6 Adapter, beta chain (SEQ ID NO: 740)Scaffolding, Modulator Proteins P07437 TUBB Tubulin 310-318 YLTVAAVFR 6Adapter, beta chain (SEQ ID NO: 741) Scaffolding, Modulator ProteinsP07437 TUBB Tubulin 337-350 NSSYFVEWIPNNVK 13 3 9 Adapter, beta chain(SEQ ID NO: 742) 8 6 Scaffolding, Modulator Proteins P07437 TUBB Tubulin381-390 ISEQFTAMFR (SEQ ID NO: 743) 6 Adapter, beta chain Scaffolding,Modulator Proteins P07437 TUBB Tubulin 47-58 ISVYYNEATGGK 13 6 Adapter,beta chain (SEQ ID NO: 744) Scaffolding, Modulator Proteins P07437TUBB Tubulin 63-77 AILVDLEPGTMDSVR 6 Adapter, beta chain(SEQ ID NO: 745) Scaffolding, Modulator Proteins Q9BVA1 TUBB2B 381-390ISEQFTAMFR (SEQ ID NO: 746) 6 Adapter, Tubulin beta-2B Scaffolding,chain Modulator Proteins Q9BVA1 TUBB2B 63-77 AILVDLEPGTMDSVR 6 Adapter,Tubulin beta-2B (SEQ ID NO: 747) Scaffolding, chain Modulator ProteinsQ9BVA1 TUBB2B 175-213 VSDTVVEPYNATLSVHQLVENTD 6 Adapter, Tubulin beta-2BETYCIDNEALYDICFR Scaffolding, chain (SEQ ID NO: 748) Modulator ProteinsQ9BVA1 TUBB2B 337-350 NSSYFVEWIPNNVK 3 13 9 Adapter, Tubulin beta-2B(SEQ ID NO: 749) 8 6 Scaffolding, chain Modulator Proteins Q9BVA1 TUBB2B104-121 GHYTEGAELVDSVLDVVR 9 6 Adapter, Tubulin beta-2B (SEQ ID NO: 750)Scaffolding, chain Modulator Proteins Q9BVA1 TUBB2B 217-241LTTPTYGDLNHLVSATMSGCTTC 3 13 Adapter, Tubulin beta-2BLR (SEQ ID NO: 751) Scaffolding, chain Modulator Proteins Q13509TUBB3 Tubulin 104-121 GHYTEGAELVDSVLDVVR 9 4 6 Adapter, beta-3 chain(SEQ ID NO: 752) Scaffolding, Modulator Proteins Q13509 TUBB3 Tubulin337-350 NSSYFVEWIPNNVK 4 6 Adapter, beta-3 chain (SEQ ID NO: 753)Scaffolding, Modulator Proteins Q13509 TUBB3 Tubulin 63-77AILVDLEPGTMDSVR 4 Adapter, beta-3 chain (SEQ ID NO: 754) Scaffolding,Modulator Proteins P68371 TUBB4B  104-121 GHYTEGAELVDSVLDVVR 9 6Adapter, Tubulin beta-4B (SEQ ID NO: 755) Scaffolding, chain ModulatorProteins P68371 TUBB4B  175-213 VSDTVVEPYNATLSVHQLVENTD 6 Adapter,Tubulin beta-4B ETYCIDNEALYDICFR Scaffolding, chain (SEQ ID NO: 756)Modulator Proteins P68371 TUBB4B  217-241 LTTPTYGDLNHLVSATMSGVTTC 3 13 6Adapter, Tubulin beta-4B LR (SEQ ID NO: 757) Scaffolding, chainModulator Proteins P68371 TUBB4B  310-318 YLTVAAVFR (SEQ ID NO: 758) 6Adapter, Tubulin beta-4B Scaffolding, chain Modulator Proteins P68371TUBB4B  337-350 NSSYFVEWIPNNVK 3 13 9 Adapter, Tubulin beta-4B(SEQ ID NO: 759) 8 6 Scaffolding, chain Modulator Proteins P68371TUBB4B  381-390 ISEQFTAMFR (SEQ ID NO: 760) 6 Adapter, Tubulin beta-4BScaffolding, chain Modulator Proteins Q9BUF5 TUBB6 Tubulin 217-241LTTPTYGDLNHLVSATMSGVTTS 4 Adapter, beta-6 chain LR (SEQ ID NO: 761)Scaffolding, Modulator Proteins Q9BUF5 TUBB6 Tubulin 175-213VSDTVVEPYNATLSVHQLVENTD 6 Adapter, beta-6 chain ETYCIDNEALYDICFRScaffolding, (SEQ ID NO: 762) Modulator Proteins Q9BUF5 TUBB6 Tubulin337-350 NSSYFVEWIPNNVK 4 2 13 Adapter, beta-6 chain (SEQ ID NO: 763) 6Scaffolding, Modulator Proteins P49411 TUFM 183-200 ADAVQDSEMVELVELEIR13 4 3 Transciption Elongation (SEQ ID NO: 764) 2 8 6 factors,factor Tu,  Regulators mitochondrial P49411 TUFM 239-252 LLDAVDTYIPVPAR6 Transciption Elongation (SEQ ID NO: 765) factors, factor Tu, Regulators mitochondrial P49411 TUFM 272-281 GTVVTGTLER (SEQ ID NO: 766)3 4 15 Transciption Elongation 6 8 factors, factor Tu,  Regulatorsmitochondrial Q9BRA2 TXNDC17 42477 YEEVSVSGFEEFHR 14 UncategorizedThioredoxin (SEQ ID NO: 90) domain- containing protein 17 Q14157 UBAP2L239-257 TATEEWGTEDWNEDLSETK 8 Uncategorized Ubiquitin- (SEQ ID NO: 767)associated protein 2-like P31930 UQCRC1 397-415 NALVSHLDGTTPVCEDIGR13 4 3 Channels, Cytochrome b- (SEQ ID NO: 768) 2 8 Transporters,c1 complex Receptors subunit 1, mitochondrial P21796 VDAC1 140-161GALVLGYEGWLAGYQMNFETAK 14 2 Channels, Voltage- (SEQ ID NO: 769) 13 4 6Transporters, dependent Receptors anion-slective channel protein P21796VDAC1 121-139 EHINLGCDMDFDIAGPSIR 13 14 Channels, Voltage-(SEQ ID NO: 770) 2 4 8 Transporters, dependent Receptors anion-slectivechannel protein P21796 VDAC1 75-93 WNTDNTLGTEITVEDQLAR 13 14 Channels,Voltage- (SEQ ID NO: 771) 15 3 2 Transporters, dependent 4 6 9 Receptorsanion-slective 8 channel protein P21796 VDAC1 164-174VTQSNFAVGYK (SEQ ID NO: 772) 14 4 8 Channels, Voltage- 6 Transporters,dependent Receptors anion-slective channel protein P21796 VDAC1 64-74WTEYGLTFTEK (SEQ ID NO: 773) 13 14 Channels, Voltage- 15 3 2Transporters, dependent 4 6 9 Receptors anion-slective 8 channel proteinP21796 VDAC1 35-53 SENGLEFTSSGSANTETTK 4 8 9 Channels, Voltage-(SEQ ID NO: 774) Transporters, dependent Receptors anion-slectivechannel protein P21796 VDAC1 175-197 TDEFQLHTNVNDGTEFGGSIYQK 14 4 8Channels, Voltage- (SEQ ID NO: 775) Transporters, dependent Receptorsanion-slective channel protein P21796 VDAC1 225-236 YQIDPDACFSAK  4 8Channels, Voltage- (SEQ ID NO: 776) Transporters, dependent Receptorsanion-slective channel protein P45880 VDAC2 86-107WNTDNTLGTEIAIEDQICQGLK 13 14 Channels, Voltage- (SEQ ID NO: 777) 15 3 2Transporters, dependent 4 6 9 Receptors anion-slective 8 channel proteinP45880 VDAC2 178-185 NNFAVGYR (SEQ ID NO: 778) 14 2 Channels, Voltage-13 8 4 Transporters, dependent 6 Receptors anion-slectivechannel protein P45880 VDAC2 186-208 TGDFQLHTNVNDGTEFGGSIYQK 14 4 2Channels, Voltage- (SEQ ID NO: 779) Transporters, dependent Receptorsanion-slective channel protein P45880 VDAC2 209-229VCEDLDTSVNLAWTSGTNCTR 13 14 Channels, Voltage- (SEQ ID NO: 780) 15 2 9Transporters, dependent 8 4 Receptors anion-slective channel proteinP45880 VDAC2 236-247 TQLDPTASISAK  13 14 Channels, Voltage-(SEQ ID NO: 781) 4 Transporters, dependent Receptors anion-slectivechannel protein P45880 VDAC2 75-85 WCEYGLTFTEK (SEQ ID NO: 782) 13 14Channels, Voltage- 15 3 2 Transporters, dependent 4 6 9 Receptorsanion-slective channel protein Q9Y277 VDAC3 164-174LSQNNFALGYK (SEQ ID NO: 783) 14 Channels, Voltage- Transporters,dependent Receptors anion-slective channel protein P08670 VIM Vimentin283-292 NLQEAEEWK (SEQ ID NO: 784) 13 14 Uncategorized 3 2 4 15 6 9 8P08670 VIM Vimentin 322-334 QVQSLTCEVDALK 4 9 6 Uncategorized(SEQ ID NO: 785) P08670 VIM Vimentin 176-184 DNAEDIMR (SEQ ID NO: 786) 6Uncategorized P08670 VIM Vimentin 197-207 EEAENTLQSFR (SEQ ID NO: 787)13 14 Uncategorized 3 2 15 9 6 P08670 VIM Vimentin 130-139ILLAELEQLK (SEQ ID NO: 788) 14 3 2 Uncategorized   4 69 P08670VIM Vimentin 29-36 SYVTTSTR (SEQ ID NO: 789) 14 6 Uncategorized P08670VIM Vimentin 146-155 LGDLYEEEMR (SEQ ID NO: 790) 6 Uncategorized P08670VIM Vimentin 42502 SVSSSSYR (SEQ ID NO: 791) 6 Uncategorized P08670VIM Vimentin 189-196 LQEEMLQR (SEQ ID NO: 792) 3 6 Uncategorized P08670VIM Vimentin 105-113 VELQELNDR (SEQ ID NO: 793) 4 6 Uncategorized P08670VIM Vimentin 79-97 LLQDSVDFSLADAINTEFK 13 14 Uncategorized(SEQ ID NO: 794) 15 4 3 2 6 9 8 P08670 VIM Vimentin 295-304FADLSEAANR (SEQ ID NO: 795) 6 Uncategorized P08670 VIM Vimentin 346-364EMEENFAVEAANYQDTIGR 13 14 Uncategorized (SEQ ID NO: 796) 15 3 2 4 6 9 8P08670 VIM Vimentin 335-342 GTNESLER (SEQ ID NO: 797) 6 UncategorizedP08670 VIM Vimentin 114-120 GANYIDK (SEQ ID NO: 798) 4 3 8 Uncategorized6 P08670 VIM Vimentin 365-373 LQDEIQNMK (SEQ ID NO: 799) 4 3 2Uncategorized 6 P08670 VIM Vimentin 382-390 EYQDLLNVK(SEQ ID NO: 800) 3Uncategorized P08670 VIM Vimentin 51-64 SLYASSPGGVYATR Uncategorized(SEQ ID NO: 801) 14 2 4 3 13 8 6 P08670 VIM Vimentin 224-235VESLQEEIAFLK  14 4 6 Uncategorized (SEQ ID NO: 802) Q96GC9 VMP1 Vacuole214-243 LSGAEPDDEEYQEFEEMLEHAES 14 Uncategorized membraneAQDFASR (SEQ ID NO: 803) protein 1 Q96AX1 VPS33A 233-262NVDLLTPLATQLTYEGLIDEIYGIQ 14 Channels, Vacuolar proteinNSYVK (SEQ ID NO: 804) Transporters, sorting- Receptors associatedprotein 33A Q9UID3 VPS51 Vacuolar 742-763 FVADEELVHLLLDEVVASAALR 14Channels, protein sorting- (SEQ ID NO: 805) Transporters, associatedReceptors protein 51 hom O43592 XPOT Exportin- 825-843VLVTVIQGAVEYPDPIAQK 132 Channels, T (SEQ ID NO: 806) Transporters,Receptors P12956 XRCC6 X-ray 475-488 SDSFENPVLQQHFR 3 4 2 Transcriptionrepair cross- (SEQ ID NO: 807) 13 8 factors, complementing Regulatorsprotein 6 P12956 XRCC6 X-ray 489-510 NLEALALDLMEPQAVDLTLPK 13 3 2Transcription repair cross- (SEQ ID NO: 808) 4 8 factors, complementingRegulators protein 6 P67809 YBX1 102-118 SVGDGETVEFDVVEGEK 6Transcription Nuclease- (SEQ ID NO: 809) factors, sensitive Regulatorselement-binding protein 1 P62258 YWHAE 14-3-3 197-215AAFDDAIAELDTLSEESYK 13 Uncategorized protein epsilon (SEQ ID NO: 92)P62258 YWHAE 14-3-3 143-153 EAAENSLVAYK 13 Uncategorized protein epsilon(SEQ ID NO: 91) P27348 YWHAQ 14-3-3 194-212 TAFDEAIAELDTLNEDSYK 14Uncategorized protein theta (SEQ ID NO: 93) P63104 YWHAZ 14-3-3 194-212TAFDEAIAELDTLSEESY 14 13 Uncategorized protein (SEQ ID NO: 94)zelta/delta

TABLE 2 Predicted Overlapping pocket pockets Labeled residue (fpocketProtein Name Peptide Peptide Sequence Probes PDB overlap designation)ACP1 Low 42-59 VDSAATSGYEIGNPPD 13 3N8I 47.A,50.A 1 molecular weight YRphosphotyrosine (SEQ ID NO: 1) protein phosp ADCK3 Chaperone 277-295LGQMLSIQDDAFINPH 14 4PED 278.A,283.A 1 activity of bc1 LAK complex-like,(SEQ ID NO: 2) mitochondr ADK Adenosine 209-224 IFTLNLSAPFISQFYK 2 4O1L200.A,205.A, 1, 5, 10, 12, kinase (SEQ ID NO: 3) 207.A,200.B, 20, 21201.B,206.B, 207.B ADSS 431-441 FIEDELQIPVK 14 2V40 435.A 8Adenylosuccinate (SEQ ID NO: 4) synthetase isozyme 2 AHCYL2 Putative331-342 GIVEESVTGVHR (SEQ 6 3GVP 335.A,336.A, 5, 6, 16, 17,adenosylhomocysteinase ID NO: 810) 337.A,338.A, 18, 22, 27, 3341.A,342.A, 38, 51 335.B, 336.B,337.B, 338.B,332.C. 334.C, 335.C,337.C,339.C,342.C, 332.D,334.D, 335.D,336.D, 337.D, 339.D,342.DAIFM1 Apoptosis- 475-510 PYWHQSMFWSDLGP 2 3 4 6 4LII 480.A,482.A, 1inducing factor 1, DVGYEAIGLVDSSLPT 492.A mitochondrial VGVFAK(SEQ ID NO: 5) ALDH7A1 Alpha- 139-162 ILVEGVGEVQEYVDIC 8 13 4ZUL117.A,118.A, 3, 6, 26, 37 aminoadipic DYAVGLSR 1220.A,123.A, 47, 48, 52,semialdehyde (SEQ ID NO: 6) 127.A,l28.A, 69, 71, 84, dehydrogenase130.A, 86, 93, 95, 131.A,132.A, 102, 115 133.A,134.A, 111.B,112.B,113.B, 114.B,117.B, 120.B,123.B, 127.B,128.B, 130.B, 132.B,133.B,134.B,120.C, 123.C,127.C, 128.C, 120.D,123.D, 127.D,128.D, 130.D,132.D,133.D, 134.D,116.E, 120.E,124.E, 128.E,120.F, 127.F,128.F, 130.F,131.F,132.F, 133.F,134.F, 128.G,130.G, 132.G,133.G, 134.G,120.H, 124.H,128.H,130.H, 133.H,134.H ANP32A Acidic 117-132 SLDLFNCEVTNLNDY 13 4XOSNo Overlap — leucine-rich nuclear R (SEQ ID NO: 811) phosphoprotein 32fami API5 Apoptosis 182-196 VLEDVTGEEFVLFMK 4 3U0R 187.A,193.A 3inhibitor 5 (SEQ ID NO: 812) API5 Apoptosis 131-148 GTLGGLFSQILQGEDI 43U0R 145.A 3 inhibitors VR (SEQ ID NO: 813) API5 Apoptosis 211-237QQLVELVAEQADLEQ inhibitor 5 TFNPSDPDCVDR (SEQ 4 3U0R No Overlap —ID NO: 814) ARF1 ADP- 39-59 LGEIVTTIPTIGFNVET 2 3 8 13 3O47 175.A,176.A,1, 2, 9, 11, 15 ribosylation factor 1 VEYK 177.A,178.A, (SEQ ID NO: 7)179.A,181.A, 183,A, 185.A,172.B, 173.B,174.B, 185.B,187.B, 189.BARF4 ADP- 39-59 LGEIVTTIPTIGFNVET 2 3 8 13 1Z6X 48.A,49.A,50.A, 1, 5, 6ribosylation factor 4 VEYK 51.A,52.A, (SEQ ID NO: 7) 54.A,49.B,52.B,54.B ARF5 ADP- 39-59 LGEIVTTIPTIGFNVET 2 3 4 8 2B6H 44.A,52.A,53.A,ribosylation factor 5 VEYK 13 54.A,57.A, 1, 2 (SEQ ID NO: 7) 59.AARL1 ADP- 163-178 GTGLDEAMEWLVET 13 14 4DCN No Overlap —ribosylation factor- LK like protein 1 (SEQ ID NO: 9) ARL1 ADP- 37-59LQVGEVVTTIPTIGFN 13 4DCN 38.A,44.A,4.6A, 1, 2, 3, 4 ribosylation factor-VETVTYK 47.A,51.A, like protein 1 (SEQ ID NO: 10) 52.A,53.A, 54.A,38.B,43.B,44.B, 46.B,47.B, 48.B,52.B, 54.B ATIC Bifunctional 178-194AFTHTAQYDEAISDY 13 1PKX 183.A,184.A, 5, 12, 17, 18, purine biosynthesisFR 187.A,191.A, 49, 51, 54 protein PURH (SEQ ID NO: 11) 194.A,183.B,187.B, 188.B,190.B, 191.B,194.B, 180.C,181.C, 183.C, 184.C,185.C,187.C,188.C, 191.C, 194.C,181.D, 183.D,184.D, 185.D,187.D, 188.D,190.D,194.D BAX Apoptosis 66-78 IGDELDSNMELQR 13 4ZIG No Overlap —regulator BAX (SEQ ID NO: 815) BLMH Bleomycin 203-218 GEISATQDVMMEEIFR13 1CB5 210.A,213.A, 29, 30, 31, 78 hydrolase (SEQ ID NO: 13)217.A,218.A, 210.B, ″ ' 213.B,217.B, 210.C,213.C, 217.C BLMH Bleomycin111-124 CYFFLSAFVDTAQR 14 1CB5 112.A,122.A, 4, 29, 30, 31 hydrolase(SEQ ID NO: 12) 123.A,112.B, 67, 76, 77 113.B, 122.B,123.B, 112.C,122.C,123.C C1QBP 247-276 GVDNTFADELVELST 3 9 13 3RPX 264.A,265.A, 1, 2, 6, 8Complement ALEHQEYITFLEDLK 14 268.A,274.A, component 1 Q(SEQ ID NO: 816) 260.C,261.C, subcomponent- 264.C, binding prot265.C,268.C C1QBP 105-119 MSGGWELELNGTEA 9 3RPX 108.A,110. 7 ComplementK (SEQ ID NO: 817) A,111.A component 1 Q subcomponent- binding protCALM3 39-75 SLGQNPTEAELQDMI 14 4UPU No Overlap — CalmodulinNEVDADGNGTIDFPE FLTMMAR  NO: 818) CALR Calreticulin 323-351SGTIFDNFLITNDEAY 6 9 13 3POW 329.A,345.A, AEEFGNETWGVTK 346.A,349.A 4(SEQ ID NO: 14) CALR Calreticulin 99-111 HEQNIDCGGGYVK 6 3POW No Overlap— (SEQ ID NO: 15) CAPN1 Calpain-1 175-193 LVFVHSAEGNEFWSA 14 2ARY175.A,179.A, 1, 14 catalytic subunit LLEK 180.A,181.A, (SEQ ID NO: 16)182.A,183.A, 186.A, 175.B,176.B, 179.B,180.B, 181.B,186.B CKB Creatine224-236 TFLVWVNEEDHLR 3 3B6R 228.A,232.A, 1, 2, 4 kinase B-type(SEQ ID NO: 19) 233.A,228.B, 232.B CKB Creatine 342-358 LGFSEVELVQMVVDG3 13 3B6R 342.A 21 kinase B-type VK (SEQ ID NO: 21) CKB Creatine 367-381LEQGQAIDDLMPAQK 13 3B6R No Overlap — kinase B-type (SEQ ID NO: 22)CKB Creatine 14-32 FPAEDEFPDLSAHNN 3 3B6R 29.B 5 kinase B-type HMAK(SEQ ID NO: 17) CKB Creatine 157-172 LAVEALSSLDGDLAG 13 3B6R159.B,160.B, 3, 10, 15 kinase B-type R 163.B,164.B, (SEQ ID NO: 18)168.B,169.B, 170.B, 171.B,172.B CKB Creatine 253-265 FCTGLTQIETLFK 133B6R 261.A,265.A, 7, 17 kinase B-type (SEQ ID NO: 20) 261.B,265.BCKMT1B Creatine 257-269 SFLIWVNEEDHTR 3 1QK1 223.B,227.B, 4, 6, 38, 78,kinase U-type, (SEQ ID NO: 23) 223.C,221.D, 80, 82 mitochondria'223.D,226.D, 221.H, 223.H,226.H CLPP Putative 215-226 QSLQVIESAMER 61TG6 166.A,167.A, 20, 41, 49, ATP-dependent Clp (SEQ ID NO: 24)168.A,169.A, 53, 56, 58, protease proteolyticsu 170.A,169.B, 60, 62, 65170.B, 159.C,167.C, 168.C,169.C, 170,C,159.E, 159.G, 161.G,163.G,165.G,167.G, 168.G,169.G, 170.G COPS4 COP9 154-170 LYLEDDDPVQAEAYI 13 154D18 157.D,158.D 178 signalosome NR (SEQ ID NO: 819) complex subunit 4CSNK1A1 Casein 84-106 DYNVLVMDLLGPSLE 14 5FQD 95.C,100.C,14, 15, 69, 88, kinase I isoform DLFNFCSR 88.F,90.F, alpha(SEQ ID NO: 25) 91.F,93.F,94.F, 95.F,99.F CSNK2B Casein 112-134VYCENQPMLPIGLSDI 14 4NH1 126.C,126.D 1, 4 kinase II subunit  PGEAMVKbeta (SEQ ID NO: 26) CTNNB1 Catenin 648-661 NEGVATYAAAVLFR 13 14 3TX7660.A,661.A 28 beta-1 (SEQ ID NO: 820) CTSB Cathepsin B 315-331GQDHCGIESEVVAGIP 2 49 13 3K9M 237.A,238.A, 4, 10, 13, 19 R 240.A,241.A,(SEQ ID NO: 27) 251.A,252.A, 251.B,252.B CTSD Cathepsin D 236-253DPDAQPGGELMLGGT 9 4OD9 173.B 10 DSK (SEQ ID NO: 28) CTSD Cathepsin D288-309 EGCEAIVDTGTSLMV 4 6 8 9 4OD9 231.B,233.B, 1, 2, 7 GPVDEVR 13 14234.B,238.B, (SEQ ID NO: 29) 15 241.B,242.B, 245.B, 231.D,233.D,234.D,235.D, 236.D,238.D CTSD Cathepsin D 314-331 AIGAVPLIQGEYMIPC2 3 4 6 4OD9 258.B,260.B, 1, 2 EK 8 9 13 258.D,260.D (SEQ ID NO: 30)14 15 CYB5R3 NADH-cytochrome b5 235-241 LWYTLDR 3 lUMK 237.A,238.A, 1reductase 3 (SEQ ID NO: 31) 239.A DECR1 2,4- 299-315 FDGGEEVLISGEFNDL 61W6U 306.A,307.A, 1, 2, 9, 10, dienoyl-CoA R 308.A,309.A, 14, 23, 25,reductase, (SEQ ID NO: 32) 311.A,312.A, 27, 35, 42, 47 mitochondrial313.A, 314.A,315.A, 304.B,305.B, 308.B,310.B, 311.B, 313.B,314.B,315.B,303.C, 304.C,305.C, 306 C, 308.C,310.C, 311.C,312.C, 315.C,305.D,306.D, 307.D,308.D, 309.D,310.D, 311.D,312.D, 313.D, 314.D,315.DDHX9 ATP- 448-456 ISAVSVAER 3 3LLM 449.B,453.B, 6 dependent RNA(SEQ ID NO: 33) 456.B helicase A DIABLO Diablo 124-140 MNSEEEDEVWQVIIG13 4TX5 78.A,82.A,85.A, 5, 11, 12 homolog, AR (SEQ ID NO: 821)71.B,74.B, mitochondrial 75.B,78.B, 84.B DLD Dihydrolipoyl 450-482VLGAHILGPGAGEMV 4 13 14 3RNM 416.A,417.A, 2, 3, 8, 9, 10, dehydrogenase,NEAALALEYGASCED 418.A,423.A, 11, 12, 17, mitochondrial IAR 424.A,443.A,37, 44, 50, (SEQ ID NO: 34) 444.A, 54, 67 445.A,446.A, 447.A,415.B,416.B,423.B, 424 B, 428.B,433.B, 436.B,437.B, 446.B,421.C, 423.C,424.C,427.C, 436.C,437.C, 443.C,447.C, 421.D, 423.D,424.D, 446.DECH1 Delta(3,5)- 197-211 EVDVGLAADVGTLQ 3 4 6 8 2VRE 171.A,174.A,1, 3, 4, 24 Delta(2,4)-dienoyl- R 13 14 171.B,176.B, CoA isomerase,(SEQ ID NO: 37) 15 179.B,180.B, mitoc 171.C,174.C ECH1 Delta(3,5)-149-158 YQETFNVIER 6 2VRE 123.A,124.A, 1, 2, 3, 4, 5,Delta(2,4)-dienoyl- (SEQ ID NO: 36) 128.A,131.A, 8, 9, 12 CoA isomerase,123.B,125.B, mitoc 126.B, 128.B,131.B, 123.C,124.C, 125.C,128.C, 131.CECH1 Delta(3,5)- 113-131 MFTAG1DLMDMASDI 6 2VRE 98.A,100.A, 1, 3, 4, 12,Delta(2,4)-dienoyl- LQPK 101.A,102.A, 23, 24 CoA isomerase,(SEQ ID NO: 35) 92.B,97.B, mitoc 98.B,100.B, 90.C,92.0, 93.C,94.C,95.C,97.C, 98.C,100.C, 101.C,104.C EIF4A1 Eukaryotic 69-82GYDVIAQAQSGTGK 9 13 14 2ZU6 75.A,76.A, 1, 5, 10, 53,initiation factor 4A- (SEQ ID NO: 39) 78.A,82.A, 84 I 75.C,78.C,79.C,80.C,82.C EIF4A1 Eukaryotic 178-190 MFVLDEADEML SR 13 2ZU6178.C,190.C,1 2, 4, 5 initiation factor 4A- (SEQ ID NO: 38) 85.D,186.D,I 188.D,189.D, 190.D EIF4A2 Eukaryotic GYDVIAQAQSGTGK 13 3BOR 76.A,82.A,1 initiation factor 4A- 70-83 (SEQ ID NO: 40) 83.A II ELAVL1 ELAV- 20-37TNLIVNYLPQNMTQD 2 4 13 4FXV 33.A,26.B, 1, 2, 4, 5, 6 like protein 1ELR (SEQ ID NO: 822) 28.B,30.B, 32.B,34.B, 35.B,37.B,20.C, 21.C,32.D,34.D,35.D,37.D ERH Enhancer of 18-34 TYADYESVNECMEG 13 2NML 18.A 2rudimentary VCK (SEQ ID NO: 823) homolog ETFB Electron 36-51HSMNPFCEIAVEEAV 3 2A1T 36.S,37.S, 1, 4 transfer R 39.S,40.S,flavoprotein subunit (SEQ ID NO: 41) 41.S,43.S,44.S betaEXO1 Exonuclease 139-160 SQGVDCLVAPYEADA 2 6 8 9 3QEB 143.Z,144.Z,1, 9, 11 1 QLAYLNK 13 145.Z,149.Z, (SEQ ID NO: 95) 150.Z FARSB 72-82YDLLCLEGLVR (SEQ 9 3L4G 72.B,72.D, 1, 5, 8, 9, 43, Phenylalanine--ID NO: 824) 76.D,72.F, tRNA ligase beta 76.F,72.H,72.J, subunit74.J,76.J,75.L,  44, 45, 53, 76.N,78.N, 57, 99, 113, 72.P,75.P,124, 273, 279 76.P FARSB 518-530 IMQLLDVPPGEDK 2 3L4G 519.B,520.B,2, 7, 35, 54, Phenylalanine-- (SEQ ID NO: 825) 524.B,526.B,97, 106, 107, tRNA ligase beta 528.B,530.B, 134, 136, subunit 520.D,181, 215, 521.D,523.D, 218, 224, 524.D,525.D, 267, 288, 530.D,519.F,295, 308 520.F, 523.F,524.F, 525.F,520.H, 521.H,523.H, 524.H,526.H,530.H, 519.J,520.J, 523.J,524.J, 525.J,526.J, 529.J,530.J, 523.N,520.P,523.P FDFT1 Squalene 78-92 ALDTLEDDMTISVEK 15 3VJ9 80.A,83.A 1 synthase(SEQ ID NO: 826) FECH 254-272 SEVVILFSAHSLPMSV 4 3HCN 255.A,263.A,1, 2, 3, 8, 12, Ferrochelatase, VNR 270.A,271.A, 17, 21, 27mitochondrial (SEQ ID NO: 42) 754.B,755.B, 763.B, 764.B,766.B,768.B,770.B, 771.B FKBP4 Peptidyl- FEIGEGENLDLPYGLE 13 4LAY No Overlap —prolyl cis-trans 190-206 R (SEQ ID NO: 827) isomerase FKBP4 GLA Alpha-241-252 SILDWTSFNQER 9 3S5Z 244.A,247.A, 11, 20 galactosidase A(SEQ ID NO: 43) 250.B,251.B, 252.B GLA Alpha- 68-82 LFMEMAELMVSEGW70.A,68.B, 13, 16 galactosidase A K 4 3S5Z 71.B (SEQ ID NO: 45)GLA Alpha- 50-67 FMCNLDCQEEPDSCIS 9 3S5Z 50.A,51.A, 1, 3, 13, 16galactosidase A EK 52.A,53.A, (SEQ ID NO: 44) 59.A,60.A, 61.A,62.A,66.A,50.B, 51.B,52.B,53.B, 55.B,59.B, 60.B,61.B, 62.B,63.B, 65.B,67.BGLB1 Beta- 286-299 TEAVASSLYDILAR 9 3THC No Overlap — galactosidase(SEQ ID NO: 46) GLO1 160-179 GLAFIQDPDGYWIEIL 3 14 3W0T 159.A,164.A,1, 2, 4, 8, 12, Lactoylglutathione NPNK 165.A,166.A, 19 lyase(SEQ ID NO: 47) 175.A,178.A, 160.B, 162.B,170.B, 172.B,160.C,162.C,170.C, 172.C, 162.D,164.D, 166.D,167.D, 168.D,170.D, 172.DGLUD1 Glutamate 481-496 HGGTIPIVPTAEFQDR 6 1L1F 443.A,440.B, 35, 39, 66dehydrogenase 1, (SEQ ID NO: 49) 443.B,439.F, mitochondria 443.FGLUD1 Glutamate 152-162 YSTDVSVDEVK 6 1L1F 99.A,100.A, 4, 17, 44, 55,dehydrogenase 1, (SEQ ID NO: 48) 101.A,102.A, 57, 60, 61, 65mitochondrial 99.B,100.B, 101.B,107.B, 99.C,101.C, 102.C,99.D,100.D,101.D, 102.D, 109.D,99.E, 100.E,101.E, 102.E,99.F, 100.F,101.F,102.F,109.F GOLPH3 Golgi 75-90 EGYTSFWNDCISSGLR 14 3KN1 76.A,79.A,1, 5, 9 phosphoprotein 3 (SEQ ID NO: 50) 80.A,81.A,83.A, 84.A,85.A,87.A,90.A GSTP1 Glutathione 56-71 FQDGDLTLYQSNTILR 2 2A2R 61.B,63.B,1, 14 S-transferase P (SEQ ID NO: 51) 64.B H2AFZ Histone 47-75VGATAAVYSAAILEY 3 5FUG 48.A,49.A, 1, 2, 3, 4, 5, H2A.Z LTAEVLELAGNASK52.A,53.A, 7, 8, 10, 11, (SEQ ID NO: 828) 71.A,72.A,73.A, 18, 2774.A,49.D, 67.D,70.D, 71.D,46.G, 54.G,57.G, 59.G,60.G, 63.G,71.G,72.G,73.G, 74.G,48.J, 49.J,52.J HADH 250-271 LGAGYPMGPFELLDY 2 13 3HAD238.A,239.A, 1, 2, 3 Hydroxyacyl- VGLDTTK (SEQ ID 240.A,242.A,coenzyme A NO: 829) 243.A,252.A, dehydrogenase, 256.A, mitochondria257.A,239.B, 240.B,242.B, 243.B,245.B, 252.B, 253.B,256.B, 257.BHARS Histidine-- 170-193 EFYQCDFDIAGNFDP 4 14 15 4PHC 171.A,173.A,1, 2, 4, 5, 32, tRNA ligase, MIPDAECLK(SEQ ID 171.B,172.B, 43cytoplasmic NO: 830) 173.B,171.C, 172.C, 173.C,177.C, 180.C,181.C,182.C,184.C, 185.C, 188.C,170.D, 171.D,172.D HBA2 Hemoglobin 18-32VGAHAGEYGAEALE 4 4X0L 27.A,31.A 6 subunit alpha R (SEQ ID NO: 52)HBA2 Hemoglobin 94-100 VDPVNFK 4 4X0L 96.A 2 subunit alpha(SEQ ID NO: 53) HEXA Beta- 489-499 LTSDLTFAYER 9 2GJX 497.E,497.H,47, 70 hexosaminidase (SEQ ID NO: 54) 498.H subunit alphaHLA-A HLA class 46-59 FIAVGYVDDTQFVR 14 5EU3 23.A,30.A, 1, 5I histocompatibility  (SEQ ID NO: 831) 31.A,32.A antigen, A-2 alphaHMOX2 Heme 48-55 AENTQFVK 2 3 4 6 4WMH 52.A,54.A 1 oxygenase 2(SEQ ID NO: 55) 8 14 15 HMOX2 Heme 69-87 LATTALYFTYSALEEE 14 4WMH73.A,74.A, 1, 5 oxygenase 2 MER 76.A,77.A, (SEQ ID NO: 56) 79.A,80.AHNRNPA1 56-75 GFGFVTYATVEEVDA 3 2UP1 No Overlap - HeterogeneousAMNAR (SEQ ID NO: nuclear 832) ribonucleoprotein Al HNRNPA1 16-31LFIGGLSFETTDESLR 23 14 2UP1 27.A 2 Heterogeneous (SEQ ID NO: 833)nuclear ribonucleoprotein Al HNRNPA1 131-140 IEVIEIMTDR (SEQ ID 3 8 92UP1 No Overlap - Heterogeneous NO: 834) nuclear ribonucleoprotein AlHNRNPK 423-433 IDEPLEGSEDR (SEQ 4 1ZZK No Overlap - HeterogeneousID NO: 835) nuclear ribonucleoprotein K HNRNPK 397-405 DLAGSIIGK (SEQ ID3 4 1ZZK No Overlap - Heterogeneous NO: 836) nuclear ribonucleoprotein KHNRNPK 415-422 HESGASIK (SEQ ID 3 4 13 1ZZK 42.A 2 HeterogeneousNO: 837) nuclear ribonucleoprotein K HNRNPK 434-456 IITITGTQDQIQNAQYL2 3 4 8 1ZZK 75.A,76.A, 1, 2 Heterogeneous LQNSVK (SEQ ID NO: 9 13 1478.A,79.A, nuclear 838) 80.A ribonucleoprotein K HNRNPL 399-411VFNVFCLYGNVEK 2 3TO8 405.A,406.A 2 Heterogeneous (SEQ ID NO: 839)nuclear ribonucleoprotein L HSD17B10 3- GLVAVITGGASGLGL hydroxyacyl-CoA10-29 ATAER (SEQ ID NO: 2 3 2O23 20.A,29.A, 1, 2, 16 dehydrogenase 840)20.B,29.B type-2 HSD17B4 169-183 LGLLGLANSLAIEGR 3 1ZBQ 175.A,176.A,10, 12, 15, Peroxisomal (SEQ ID NO: 57) 179.A,180.A, 22, 44multifunctional 183.A,169.B, enzyme type 2 175.B, 176.B,169.C,172.C,176.C, 179.C,180.C, 169.D, 172.D,179.D, 180.D,183.D, 179.F,180.FHSP90AB1 Heat 360-378 VFIMDSCDELIPEYLN 13 14 3PRY 361.A,362.A,1,2, 3, 4, 5, shock protein HSP FIR 363.A,364.A, 7, 12, 30 90-beta(SEQ ID NO: 58) 365.A,366.A, 367.A, 368.A,370.A, 371.A,375.A,365.B,366.B, 367.B, 362.C,365.C, 366.C,367.C, 370.C,371.C, 372.C,373.C,375.C HSP90AB1 Heat 507-526 GFEVVYMTEPIDEYC 13 14 3PRY508.A,512.A, 1, 3, 4, 5, 6, shock protein HSP VQQLK 513.A,514.A,7, 11, 13, 18, 90-beta (SEQ ID NO: 59) 515.A,516.A, 20, 21, 25, 517.A,28, 33 518.A,519.A, 520.A,523.A, 525.A, 514.B,516.B, 518.B,525.B,508.C,512.C, 513.C,514.C, 515.C, 516.C,517.C, 518.C,519.C, 520.C,524.CHSP90B1 117-135 LISLTDENALSGNEEL 9 4NH9 No Overlap - Endoplasmin TVK(SEQ ID NO: 60) HSP90B1 271-285 YSQFINFPIYVWSSK 6 4NH9 No Overlap -Endoplasmin (SEQ ID NO: 61) HSPA1B Heat 424-447 QTQIFTTYSDNQPGVL 3 134WV5 429.A,431.A, 1, 3, 7, 10, 11 shock 70 kDa IQVYEGER (SEQ ID432.A,433.A, protein 1A/1B NO: 841) 434.A,435.A, 436.A, 439.A,444.A,436.B,439.B, 445.B,446.B, 447.B HSPA5 78 kDa 602-617 IEWLESHQDADIEDFK 65E85 602.A,605.A, 6 glucose-regulated (SEQ ID NO: 842) 606.A,609.Aprotein HSPA5 78 kDa 475-492 DNHLLGTFDLTGIPPA 6 5E85 490.A,491.A, 6, 7glucose-regulated PR (SEQ ID NO: 843) 492.A protein HSPA8 Heat shock113-126 SFYPEEVSSMVLIK 13 14 3LDQ 115.A,116.A, 15 cognate 71 kDa(SEQ ID NO: 62) 117.A protein HSPA9 Stress-70 266-284 STNGDTFLGGEDFDQ8 13 4KBO 268.A,269.A, 1, 3 protein, ALLR (SEQ ID NO: 270.A,271.A,mitochondrial 844) 279.A,283.A HSPD1 60 Da heat 206-218 TLNDELEIIEGMK3 13 4PJ1 183.A,184.A, 1, 2, 3, 4, 7, shock protein, (SEQ ID NO: 845)188.A,190.A, 14, 17, 21, mitochondrial 194.A,183.B, 27, 29, 34, 193.B,36, 37, 44, 183.C,186.C, 46, 47, 48, 188.C,190.C, 49, 53, 54,194.C,183.D, 55, 57, 58, 184.D, 60, 63, 64, 188.D,190.D, 67, 72, 73,191.D,193.D, 82, 84, 95, 183.E,184.E, 100, 103, 190.E, 117, 118,192.E,193.E, 119, 129, 183.F,184.F, 131, 135, 188.F,190.F, 154, 160,191.F,192.F, 204, 244, 193.F,183.G, 269, 277, 184.G, 281, 310,189.G,191.G, 369, 371, 193.G,183.H, 381, 382, 184.H,190.H, 385, 472194.H, 183.I,191.I, 193.I,183.J, 192.J,193.J, 183.K,184.K, 192.K,193.K,182.L,183.L, 184.L, 185.L,186.L, 187.L,188.L, 190.L,193.L, 194.L,183.M,184.M, 190.M,193.M, 183.N,184.N, 188.N,189.N, 190.N, 191.N,192.N,193.N,194.N HSPD1 60 kDa heat 222-233 GYISPYFINTSK (SEQ 13 4PJ1199.A,200. shock protein, ID NO: 846) A,201.A,202.A, mitochondrial203.A,205.A, 208.A, 18, 19, 22, 200.B,201.B, 25, 28, 30, 202.B,203.B,38, 39, 43, 204.B,205.B, 61, 98, 102, 206.B, 123, 124, 207.B,208.B,152, 179, 209.B,200.D, 184, 188, 201.D,202.D, 201, 202, 203.D, 209, 222,208.D,199.E, 229, 282, 202.E,203.E, 283, 314, 205.E,206.E, 332, 340,208.E,209.E, 388, 409, 199.F, 429, 460, 200.F,201.F, 468, 471, 482202.F,203.F, 206.F,198.G, 199.G,200.G, 201.G,202.G, 205.G, 206.G,200.H,201.H,202.H, 203.H,206.H, 207.H, 199.I,201.I, 202.I,203.I, 205.I,199.J,200.I,201.J, 202.J,203.J, 200.K,201.K, 202.K,203.K, 206.K,207K, 198.L,199.L,200.L, 202.L,203.L, 205.L,199.M, 200.M,201.M, 202.M, 203.M,205.M,208.M HSPD1 60 kDa heat 251-268 ISSIQSIVPALEIANAH 3 13 4PJ1 230.B,231.B,shock protein, R (SEQ ID NO: 847) 234.B,235.B, mitochondrial238.B,243.B, 229.C, 230.C,231.C, 234.C,235.C, 238.C,243.C, 244.C,237.E,240.E, 18, 66, 83, 241.E,244.E, 96, 147, 176, 231.F,234.F,179, 183, 235.F,238.F, 216, 217, 244.F,228.G, 305, 362, 238.G, 374, 377,240.G,241.G, 380, 391, 242.G,244.G, 439, 473, 482 237.H,240.H, 241.H,244.H,237.K, 238.K,241.K, 231.M, 240.M,241.M, 244.M,238.N, 239.N,242.N,244.N HSPD1 60 kDa heat 371-387 IQEIIEQLDVTTSEYEK 13 4PJ1 349.A,350.A,1, 2, 3, 4, 7, shock protein, (SEQ ID NO: 848) 353.A,361.A, 14, 17, 24,mitochondrial 363.A,352.B, 25, 30, 37, 353.B, 43, 46, 49, 355.B,356.B,52, 53, 54, 357.B,358.B,  55, 57, 63, 359.B,361.B, 73, 85, 95, 362.B,98, 100, 102, 363.B,348.C, 111, 118, 350.C,351.C, 128, 134, 352.C,353.C,150, 154, 354.C, 173, 181, 355.C,361.C, 184, 197, 363.C,348.D, 198, 201,349.D,350.D, 202, 206, 352.D, 222, 229, 353.D,358.D, 237, 240,361.D,362.D, 242, 278, 363.D,350.E, 280, 282, 352.E, 283, 297,353.E,354.E, 330, 332, 355.E,356.E, 353, 371, 357.E,358.E, 389, 449359.E,361.E, 362.E,363.E, 348.F, 351.F,354.F, 355.F,358.F, 361.F,363.F,348.G,361.G, 362.G,348.H, 349.H, 350.H,353.H, 355.H,361.H, 363.H,348.I,349.I,352.I, 353.I,361.I, 349.J,350.J, 351.J,353.J, 354.J,355.J,361.J,362.J, 363.J,348.K, 349.K, 353.K,354.K, 355.K,361.K, 348.L,349.L,351.L, 355.L,356.L, 358.L,361.L, 362.L,348.M, 349.M,350.M, 353.M,354.M,355.M, 361.M,362.M, 363.M HSPD1 60 kDa heat 494-516IMQSSSEVGYDAMAG 8 13 4PJ1 479.A,480.A, 5, 6, 8, 9, 10, shock protein,DFVNMVEK (SEQ ID 482.A,483.A, 11, 12, 15, mitochondrial NO: 849)479.B,481.B, 16, 33, 106, 482.B, 133, 213, 484.B,479.C, 252, 279,484.C,486.C, 334, 390, 479.E,480.E, 469, 477 481.E, 482.E,491.E,492.E,479.F, 479.G,483.G, 479.H,482.H, 483.H,484.H, 491.H, 492.I,484.J,471.K,472.K, 475.K,484.K, 479.L,481.L, 482.L, 483.L,489.L, 471.M,479.M,479.N,481.N HSPD1 60 kDa heat 97-121 LVQDVANNTNEEAG 8 13 4PJ180.A,84.A,94.A, 6, 8, 9, 10, shock protein, DGTTTATVLAR (SEQ 79.B,84.B,11, 12, 14, mitochondrial ID NO: 850) 91.B,97.B, 15, 16 ,17 80.C,84.C,20' 21' 31' 87.C,90.C, 37' 41' 46' 94.C,97.C,80.D, 48, 49, 53,82.D,84.D, 55, 56, 57, 88.D,91.D, 60, 63, 67, 75.E,76.E, 71, 73, 84,80.E,83.E,94.E, 121, 142, 80.F,84.F, 145, 178, 87.F,88.F, 181, 21490.F,80.G,82.G, 237, 240, ' 84.G,87.G, 250, 253, 90.G,94.G, 255, 275,97.G,80.H, 280, 319, 371 82.H,83.H, 85.H,86.H, 89.H,80.I,83.I,91.I,80.J, 83.J,84.J,86.J, 94.J,79.K, 83.K,84.K, 85.K,86.K,94.K,97.K, 80.L,84.L, 85.L,86.L,87.L, 94.L,97.L, 80.M,82.M, 83.M,88.M,90.M,94.M, 97.M,80.N, 82.N,84.N, 87.N,90.N IDE Insulin- 312-324NLYVTFPIPDLQK 4 4RAL 316.A,319.A, 3, 4, 7, 39, degrading enzyme(SEQ ID NO: 851) 320.A,321.A, 41, 67, 93 322.A,323.A, 324.A,316.B,319.B, 320.B IGF2BP1 Insulin- 509-525 TVNELQNLTAAEVVV 3 13 3KRM525.A,515.B, 1, 2, 12, 13, like growth factor 2  PR (SEQ ID NO: 852)518.B,524.B, 17 mRNA-binding 525.B,524.C, protein 525.CIMPDH2 Inosine-5- 110-124 YEQGFITDPVVLSPK 13 1NF7 110.A,111.A,3, 9, 16, 21, monophosphate (SEQ ID NO: 63) 112.A,113.A, 30, 33dehydrogenase 2 114.A,116.A, 120.A, 122.A,110.B, 111.B,112.B,119.B,121.B KPNA2 Importin 203-227 YGAVDPLLALLAVPD 13 14 4WV6 No Overlap— subunit alpha-2 MSSLACGYLR (SEQ ID NO: 853) KPNA2 Importin 301-315LLGASELPIVTPALR 13 4WV6 No Overlap — subunit alpha-2 (SEQ ID NO: 854)KPNB1 Importin 317-332 GALQYLVPILTQTLTK 13 14 3W5K 318.A,330.A 1,23subunit beta-1 (SEQ ID NO: 855) KPNB1 Importin 28-42 AAVENLPTFLVELSR13 14 3W5K 29.A,30.A,34.A, 28, 33, 39 subunit beta-1 (SEQ ID NO: 856)3 5.A,36.A, 38.A,39.A, 40.A,42.A KPNB1 Importin 526-537SSAYESLMEIVK (SEQ 13 14 3W5K 537.A 3 subunit beta-1 ID NO: 857)LDHA L-lactate 43-57 DLADELALVDVIEDK 9 4JNK 42.A,43.A,44.A,1, 2, 3, 4, 6, dehydrogenase A (SEQ ID NO: 64) 45.A,46.A, 7, 10, 12, 14,chain 5 1.A,42.B, 16, 27, 29 45.B,46.B, 51.B,53.B, 56.B,42.C,45.C,50.C,51.C, 42.D,43.D, 44.D,45.D, 46.D,51.D, 52.D LDHB L-lactate234-244 MVVESAYEVIK 4 1I0Z 233.A,238.A, dehydrogenase B (SEQ ID NO: 65)242.A,238.B, 1, 2, 4, 5 chain 239.B LGMN Legumain 102-118DYTGEDVTPQNFLAV 9 4N6O No Overlap — LR (SEQ ID NO: 66) LMNA Prelamin-352-366 MQQQLDEYQELLDIK 6 13 3V5B No Overlap — A/C (SEQ ID NO: 96) LTA4H366-386 LVVDLTDIDPDVAYS 4 8 13 3U9W 1367.A,1369.A, 1 Leukotriene A-4SVPYEK 1377.A, hydrolase (SEQ ID NO: 67) 1380.A,1383.A NAGLU Alpha-N-566-580 QAVQELVSLYYEEAR 9 4XWH No Overlap — acetylglucosaminidase(SEQ ID NO: 858) NAGLU Alpha-N- 594-615 AGGVLAYELLPALDE 13 15 4XWHNo Overlap — acetylglucosaminidase VLASDSR (SEQ ID NO: 859) NAMPT175-189 YLLETSGNLDGLEYK 3 6 8 13 4LVF 185.A,187.A, 2, 5, 6 Nicotinamide(SEQ ID NO: 68) 14 15 188.A,189.A, phosphoribosyltrans  184.B,185.B,ferase 189.B NCBP1 Nuclear 42-65 SACSLESNLEGLAGV 2 3 13 3FEY No Overlap— cap-binding protein LEADLPNYK (SEQ ID 14 subunit 1 NO: 860)NHP2L1 NHP2- 114-125 QQIQSIQQSIER (SEQ 236 3S1V 118.A,119.A, 4, 36, 61like protein 1 ID NO: 861) 118.J,119J, 120.J,121.J,  125.J NONO Non-POU127-135 VELDNMPLR (SEQ ID 3 3SDE 127.B,131.B 1 domain-containingNO: 862) octamer-binding protein NONO Non-POU 257-270 FAQPGSFEYEYAMR 63SDE 257.B,258.B, 6, 13 domain-containing (SEQ ID NO: 863) 259.B,260.B,octamer-binding 265.B,267.B protein NONO  Non-POU 296-304LEMEMEAAR (SEQ ID 6 3SDE No Overlap — domain-containing NO: 864)octamer-binding protein NONO Non-POU 154-176 NLPQYVSNELLEEAFS 2 3 6 93SDE 154.B,173.B, 2, 5 domain-containing VFGQVER (SEQ ID 13 14174.B,175.B octamer-binding NO: 865) protein NONO Non-POU 177-184AVVIVDDR (SEQ ID  6 3SDE 181.B,183.B, 3 domain-containing NO: 866) 184.Boctamer-binding protein NPM1 55-73 DELHIVEAEAMNYEG 13 2P1B55.A,56.A,57.A, 1, 4, 5, 7, 12, Nucleophosmin SPIK 55.B,56.B,13, 19, 23, (SEQ ID NO: 69) 66.B,67.B, 25, 27, 32, 38 68.B,72.B,55.C,56.C, 57.C,64.C,65.C, 67.C,68.C, 55.D,56.D, 57.D,61.D, 73.D,55.E,56.E,57.E, 61.E,72.E,73.E, 55.F,56.F, 57.F,64.F, 65.F,67.F,68.F,55.G,56.G, 57.G,61.G, 63 .G,64.G, 65.G,73.G, 55.H,56.H, 57.H,63.H,64.H,65.H, 55.I,56.I, 57.I,55.J,56.J, 57.J NPM1 81-101 MSVQPTVSLGGFEITP13 2P1B 81.A,82.A,83.A, 1, 9, 12, 13, Nucleophosmin PVVLR 84.A,86.A,14, 15, 16 (SEQ ID NO: 70) 87.A,88.A, 17, 25, 29, 89.A,90.A, 30, 31, 32,95.A,81.B, 33, 36, 37, 38 82.B,83.B, 84.B,86.B, 87.B,88.B,89.B,90.B,81.C, 82.C,83.C, 84.C,86.0, 87.C,88.C, 89.C,90.0, 92 C 93.C,94.C,95.C,96.C, 81.D,82.D, 83.D,84.D, 88.D,89.D, 90.D,81.E, 82.E,83.E,84.E,88.E,89.E, 90.E,93.E, 81.F,82.F, 83.F,84.F,86.F, 87.F,88.F,89.F,90.F, 94.F,95.F,97.F, 99.F,81.G, 82.G,83.G, 84.G,85.G, 86.G,88.G,89.G,90.G, 94.G,95.G, 96.G,97.G, 99.G,101.G, 81.H,82.H, 83.H,84.H,86.H,87.H, 88.H,89.H, 90.H,94.H, 95.H,96.H, 98.H,81.I, 82.I,83.I,84.I,86.I,87.I,88.I, 89.I,90.I, 95.I,96.I,81.J, 82.J,83.J,84.J, 86.J,87.J,88.J,89.J,90.J, 95.J,96.J NTMT1 N-terminal 167-185 DNMAQEGVILDDVDS 135E2B 168.A,180.A, 1, 4, 7, 18 Xaa-Pro-Lys N- SVCR (SEQ ID NO: 182.A,183.A, methyltransferase 1 867) 184.A,185.A, 167.B, 168.B,169.B,170.B,171.B, 178.B,179.B, 182.B, 183.B,184.B, 185.B OAT Ornithine332-351 VAIAALEVLEEENLAE 13 14 2OAT 340.A,341.A, 6, 21, 24, 43aminotransferase, NADK (SEQ ID NO: 344.A,346.A, mitochondrial 868)334.B,338.B, 344.B, 347.B,350.B, 340.C,341.C, 344.C,350.C P4HB Protein171-195 QFLQAAEAIDDIPFGIT 9 4JU5 178.A,179.A, 4, 13 disulfide-isomeraseSNSDVFSK (SEQ ID 181.A,181.B NO: 869) P4HB Protein 231-247HNQLPLVIEFTEQTAP 2 13 14 4JU5 231.A,232.A, 2, 3, 4, 5, 7,disulfide-isomerase K (SEQ ID NO: 870) 233.A,234.A, 11, 13, 15235.A,236.A, 242.A, 244.A,245.A, 246.A,231.B, 233.B,234.B, 235.B,238.B,239.B, 240.B,241.B, 244.B,245.B, 247.B PABPC1 114-129ALYDTFSAFGNILSCK 14 1CVJ 116.A,127.A, 1, 2, 9, 12, Polyadenylate-(SEQ ID NO: 871) 128.A,116.B, 13, 16, 27 binding protein 1 126.B,127.B,128.B, 129.B,116.C, 125.C,126.C, 127.C,128.C, 116.D, 116.E,117.E,125.E,127.E, 128.E,116.G, 126.G,128.G PABPC1 51-67 SLGYAYVNFQQPADA 3141CVJ 51.A,52.A,58.A, 2, 3, 4, 5, 7, Polyadenylate- ER (SEQ ID NO: 872)60.A,58.B, 11, 14, 22, binding protein 1 61.C,64.C, 30, 32, 33,67.C,51.E, 43, 51, 52, 53 52.E,56.E,64.E, 66.E,67.E, 52.F,60.F,60.G,67.G,51.H, 56.H,60.H PARP1 Poly 762-779 VEMLDNLLDIEVAYS 3 6 4ZZZ762.A,763.A, 1 2 29 LLR (SEQ ID NO: 873) 766.A,767.A, 769.A,773.A,763.B, 766.B,769.B PARP1 Poly 954- TTPDPSANISLDGVDV 3 4ZZZ 962.A,964.A,3, 4, 6, 8, 9, 1000 PLGTGISSGVNDTSLL 965.A,967.A, 13, 16, 22,YNEYIVYDIAQVNLK 980.A,981.A, 24, 25, 26 (SEQ ID NO: 874) 983.A,985.A,988.A, 992.A,993.A, 996.A,1000.A, 955B, 961.B,968.B, 970.B,981.B,982.B, 983.B,985.B, 986.B,988.B, 989.B,992.B, 993.B, 996.BPCMT1 Protein-L- 179-197 LILPVGPAGGNQMLE 2 3 14 1I1N 183.A,185.A 5isoaspartate(D- QYDK aspartate) O- (SEQ ID NO: 71) methyltransfPCNA Proliferating 118-138 LMDLDVEQLGIPEQE 14 5E0V 121.A,122.A, 1, 2, 11cell nuclear antigen YSCVVK (SEQ ID NO: 123.A,122.B, 875) 123.B,124.B,125.B, 126.B PDCD4 246-256 DLPELALDTPR (SEQ 13 3EIJ 256.A 1Programmed cell ID NO: 876) death protein 4 PDHB Pyruvate 53-68VFLLGEEVAQYDGAY 2 3 13 3EXE 31.B,32.B,37.B, 1,2, 3, 12, dehydrogenase ElK 14 23.D,28.D, 13, 14, 18, component subunit (SEQ ID NO: 72) 33.D,36.D,19, 21, 29 beta, 37.D,28.F, 31.F,32.F,33.F, 36.F,37.F, 24.H,28.H,31.H,32.H, 36.H,37.H PGK1 333-350 QIVWNGPVGVFEWE 3 2WZB No Overlap  —Phosphoglycerate AFAR kinase 1 (SEQ ID NO: 73) PGRMC1 106-119FYGPEGPYGVFAGR 2 34 13 4X8Y 108.A,109.A, 12 Membrane- (SEQ ID NO: 877)14 110.A associated progesterone receptor componen PKM Pyruvate 174-186IYVDDGLISLQVK 2 9 4FXF 177.D,180.D, 1, 2 4, 16, kinase isozymes(SEQ ID NO: 74) 175.C,177.C, 47, 62 M1/M2 178.C,179.C, 180.C,182.C,175.B, 177.B,180.B, 182.B PKM Pyruvate 401-422 LAPITSDPTEATAVGA2 9 4FXF 401.A,403.A, 3, 9, 37, 39, kinase isozymes VEASFK 418.A,420.A,41, 53, 68 M1/M2 (SEQ ID NO: 75) 421.A,422.A, 75, 78 401.D, 408.D,409.D,420.D,421.D, 404.C,407.C, 408.C, 409.C,410.C, 402.B,403.B, 404.B,414.BPOR NADPH-- 369-382 TALTYYLDITNPPR 13 14 3QFS 375.A,376.A 2, 5cytochrome P450 (SEQ ID NO: 76) reductase PPP1CA 133-141 IYGFYDECK 24XPN 134.C,139.C 3,4 Serine/threonine- (SEQ ID NO: 77)protein phosphatase PP1-alpha cat PPP1CC 44-60 EIFLSQPILLELEAPLK 14 4UT255.A,56.A,47.B, 13, 14 Serine/threonine- (SEQ ID NO: 79) 48.B,49.B,protein phosphatase 50.B,51.B PP1-gamma cat PPP1CC 133-141 IYGFYDECK 24UT2 No Overlap Serine/threonine- (SEQ ID NO: 78) protein phosphatase -PP1-gamma cat PPT1 Palmitoyl- 75-101 TLMEDVENSFFLNVN 2 4 8 9 3GRO75.A,76.A,78.A, 1,2, 5, 10 protein thioesterase SQVTTVCQALAK 13 1475.B,76.B, 1 (SEQ ID NO: 80) 15 80.B,81.B, 85.B,86.B, 87.B,90.B PRDX2120-127 TDEGIAYR 13 1QMV 121.A,122. 3, 5, 6, 7, 8, Peroxiredoxin-2(SEQ ID NO: 81) A,121.B,122.B, 14, 15, 18, 124.B,121.C, 20, 26, 27,122.C, 29, 30, 32, 124.C,127.C, 36, 42, 43, 120.D,121.D, 54,72, 111122.D,124.D, 126.D, 127.D,121.E, 122.E,124.E, 127.E,121.F, 122.F,124.F,127.F, 121.G,122.G, 124.G,120.H, 121.H,122.H, 124.H, 126.H,127.H,120.I,121.I, 122.I,124.I, 126.I,127.I, 120.J,121.J, 122.J,124.J,126.J,127.J PSMA2 Proteasome 144-159 PYLFQSDPSGAYFAW 2 4R3O 144.B,152.B,1 28, 63 69, subunit alpha type-2 K (SEQ ID NO: 878) 154.B,155.B, 93156.B,147.P, 149.P, 154.P,155.P, 157.P PSMA2 Proteasome 19-39LVQIEYALAAVAGGA 3 4R3O 25.P,28.P 28 subunit alpha type-2PSVGIK (SEQ ID NO: 879) PSMA4 Proteasome 68-91 LNEDMACSVAGITSD 3 6 8 134R3O 71.C,80.C,81.C, 1, 69, 93, subunit alpha type-4 ANVLTNELR (SEQID 1484.C,85.C, 145, 147 NO: 880) 88.C,70.Q, 81.Q,85.Q, 87.Q,88.Q, 89.Q,91.QPSMB1 Proteasome 129-146 FFPYYVYNIIGGLDEE 2 13 14 4R3O 107.M,108.M,4, 11, 57 subunit beta type-1 GK (SEQID NO: 881) 15 109.M,118.M,107.1,109.1 PSMB2 Proteasome 96-126 TPYHVNLLLAGYDEH 2 6 4R3O96.K,97.K,98.K, 97, 145, 180, subunit beta type-2 EGPALYYMDYLAAL99.K,101.K, 181, 191 AK (SEQ ID NO: 882) 108.K,110K 111K, 119.K,101.Y,116.Y,119.Y, 124.Y,125.Y, 126.Y PSMB2 Proteasome 42-62 ILLLCVGEAGDTVQF 64R3O 49.K,52.K,48.Y, 97, 149, 163 subunit beta type-2 AEYIQK (SEQ ID NO:54.Y,58.Y, 883) 61.Y PSMB3 Proteasome 100-115 FGPYYTEPVIAGLDPK 3 6 134R3O 100.J,106.X, 1, 3, 198 subunit beta type-3 (SEQ ID NO: 884) 14 15113.X,114.X PSMB4 Proteasome 61-80 FEGGVVIAADMLGSY 6 4R3O 30.2,35.2 67subunit beta type-4 GSLAR (SEQ ID NO: 82) PSMB5 Proteasome LLANMVYQYK3 4 6 4R3O 88.L,91.L 97 subunit beta type-5 141-150 (SEQ ID NO: 83)PSMB5 Proteasome 226-239 DAYSGGAVNLYHVR 6 4R3O No Overlap —subunit beta type-5 (SEQ ID NO: 84) PSMB6 Proteasome 80-118SGSAADTQAVADAVT 3614 4R3O 48.H,50.H,51.H, 10, 23, 50,subunit beta type-6 YQLGFHSIELNEPPLV 60.H,61.H,6 67, 152, 155, HTAASLFK4.H,65.H, 160, 169, (SEQ ID NO: 85) 67.H,68.H, 187, 200, 69.H,70.H,204, 206, 212 71.H,75.H, 77.H,78.H, 84.H,46.V, 48.V,50.V, 51.V,53.V,62.V,65.V, 70.V,72.V, 75.V,77.V, 78.V,82.V, 84.V PSPC1 Paraspeckle229-247 PVIVEPMEQFDDEDG 6 14 3SDE 229.A,231.A, 1, 2, 3, 4, 6 component 1LPEK (SEQ ID NO: 232.A,233.A, 885) 235.A,237.A, 239.A, 240.A,241.A PTGR2Prostaglandin 93-106 GDFVTSFYWPWQTK 14 2ZB4 97.A 2 reductase 2(SEQ ID NO: 886) PTGR2 262-278 DVPYPPPLSPAIEAIQK 2 3 14 2ZB4263.A,265.A, Prostaglandin (SEQ ID NO: 887) 267.A,277.A, 1, 4reductase 2 278.A RAB7A Ras-related 104-113 DEFLIQASPR 14 1YHN NoOverlap— protein Rab-7a (SEQ ID NO: 86) RARS Arginine-- 528-540 GNTAAYLLYAFTR14 4ZAJ 464.A,467.A, 1 tRNA ligase, (SEQ ID NO: 888) 468.A cytoplasmicRPL30 60S 58-68 SEIEYYAMLAK (SEQ 13 3VI6 No verlap — ribosomal proteinID NO: 889) L30 RUVBL1 RuvB- 318-333 ALESSIAPIVIFASNR 2 2XSZ229.A,231.A, 2, 3, 4, 5, 12, like 1 (SEQ ID NO: 890) 232.A,233.A,20, 37, 39, 234.A,235.A, 45, 47, 48, 236.A, 52, 53, 55, 237.A,243.A,58, 69 229.B,231.B, 232.B,233.B, 236.B, 229.C,230.C, 231.C,232.C,233.C,234.C, 235.C, 236.C,237.C, 238.C,243.C, 244.0 RUVBL1 RuvB- 91-107VPFCPMVGSEVYSTEI 2 2XSZ 105.A,106.A, 1, 2, 3, 7, 8, like 1K (SEQ ID NO: 891) 107.A,108.A, 13, 33 115.A,116.A, 117.A, 118.A,119.A,120.A,121.A, 105.B,106.B, 107.B, 108.B,120.B, 105.C,106.C, 107.C,113.C,120.0 RUVBL2 RuvB-like 2 315-330 ALESDMAPVLIMATN 14 3UK6 316.A,317.A,1, 3, 4, 5, 6, R 318.A,319.A, 7, 8, 9, 10, (SEQ ID NO: 87) 320.A,322.A,11, 12, 13, 323.A, 15, 18, 19, 329.A,315.B, 20, 22, 23, 317.B,318.B,24, 25, 30, 319.B,320.B, 31, 33, 37, 321.B, 48, 54, 64, 322.B,323.B,65, 72, 75, 329.B,315.C, 80, 83, 98, 316.C,318.C, 100, 117, 322.C,121, 147, 315.D,316.D, 154, 155 317.D,318.D, 319.D,321.D, 322.D,323.D,329.D, 318.E,319.E, 322.E,323.E, 329.E, 315.F,316.F, 317.F,318.F,319.F,320.F, 322.F,323.F, 329.F,315.G, 320.G, 329.G,330.G, 315.H,318.H,320.H,322.H, 323.H, 324.H,327.H, 329.H,315.I, 317.I,318.I, 319.I,320.I,322.I,329.I, 315.J,318.J, 320.J,322.J, 323.J,327.J, 329.J,318.K,319.K,322.K, 323.K, 325.K,328.K, 318.L,319.L, 320.L,322.L, 323.L,325.L,329.L SFPQ Splicing NL SPYVSNELLEEAFS 2 3 4 9 4WIK 377.A,380.A,1, 3, 6, 12 factor, proline- and 377-399 QFGPIER (SEQ ID NO: 13 14381.A,399.A, glutamine-rich 892) 377.B SFPQ Splicing 444-462PVIVEPLEQLDDEDGL 2 4 14 4WIK 450.A,452.A, 5, 8, 12 factor, proline- andPEK (SEQ ID NO: 893) 455.A,446.B, glutamine-rich 447.B,448.B, 449.B,455.B SLC25Al2 260-283 YGQVTPLEIDILYQLA 4 14 4P5X No Overlap —Calcium-binding DLYNASGR (SEQ ID mitochondrial NO: 894)carrier protein Aral SLC25A13 261-282 FGQVTPMEVDILFQL 2 3 4 6 4P5W262.A,263.A, 1,4, 10, 11 Calcium-binding ADLYEPR (SEQ ID 14 15264.A,265.A, mitochondrial NO: 895) 267.A,273.A, carrier protein Aral274.A, 276.A,277.A, 280.A,282.A, 261.B,262.B, 263.B, 264.B,265.B,267.B,268.B, 270.B,273.B, 274.B, 276.B,280.B SLC25A13 642-653LAVATFAGIENK (SEQ 3 4 6 8 4P5W 647.A,649.A, 1, 2, 3, 4, 8Calcium-binding ID NO: 896) 14 15 650.A,651.A, mitochondrial653.A,647.B, carrier protein Aral 648.B, 649.B,650.B, 651.BSMYD3 SET and 255-265 DQYCFECDCFR 9 5HQ8 255.A,256.A, 1, 2, 5, 6, 8,MYND domain- (SEQ ID NO: 88) 258.A,259.A, 23 containing protein 3260.A,264.A, 255.B, 256.B,258.B, 259.B SPTBN1 Spectrin 1706-EVDDLEQWIAER 13 3EDV No Overlap — beta chain, non- 1717 (SEQ ID NO: 897)erythrocytic 1 STAG2 Cohesin 273-290 ELQENQDEIENMMNA 13 4PK7 No Overlap— subunit SA-2 JFK (SEQ ID NO: 898) TIMM10 6-24 AQQLAAELEVEMMA 8 9 132BSK 15.D,19.D,20.D, 3, 11 Mitochondrial DMYNR (SEQ ID NO: 14 22.D,23.D,import inner 899) 24.D membrane translocase su TIMM44 428-439DQDELNPYAAWR 13 2CW9 434.A,435.A, 1 Mitochondrial (SEQ ID NO: 900) 438.Aimport inner membrane translocase su TNPO1 273-298 TQDQDENVALEACEF 94OO6 265.A,266.A, 3 Transportin-1 WLTLAEQPICK (SEQ 267.A ID NO: 901)TNPO1 45-64 LEQLNQYPDFNNYLIF 2 13 14 4OO6 37.A,38.A,40.A, 11, 16, 18Transportin-1 VLTK (SEQ ID NO: 43.A,45.A, 902) 46.A TPP1 Tripeptidyl-521-558 GCHESCLDEEVEGQG 4 9 13 3EDY 522.A,524. 4, 8, 13 peptidase 1FCSGPGWDPVTGWG 14 15 A,531.A,53 TPNFPALLK 2.A,534.A,5 (SEQ ID NO: 89)35.A,537.A, 540.A,541.A, 543.A,548.A TSN Translin 205-215VEEVVYDLSIR (SEQ 2 3PJA 206.A,207.A, 1, 2, 3, 4, 6, ID NO: 903)209.A,210.A, 11, 15,49, 211.A,215.A, 54, 65, 68, 207.B, 94, 101, 116211.B,213.B, 215.B,207.C, 209.C,213.C, 214.C, 215.C,206.D, 207.D,209.D,210.D,211.D, 213.D, 214.D,215.D, 207.E,211.E, 214.E,215.E, 207.F,208.F,211.F, 215.F,207.G, 210.G,211.G, 214.G,215.G, 207.H, 211.H,215.H,207.I,209.I, 211.I,213.I, 214.I,215.I TXNDC17 4-17 YEEVSVSGFEEFHR 141WOU No Overlap — Thioredoxin (SEQ ID NO: 90) domain-containingprotein 17 VDAC1 Voltage- 140-161 GALVLGYEGWLAGY 2 4 6 13 2JK4144.A,146.A, 1 2 6 dependent anion- QMNEETAK (SEQ ID 14 149.A,152.A,selective channel NO: 904) 153.A,155.A, protein 157.A VDAC1 Voltage-121-139 EHINLGCDMDFDIAG 2 4 8 13 2JK4 126.A,127.A, 1, 6 dependent anion-PSIR (SEQ ID NO: 905) 14 131.A,142.A selective channel proteinVDAC1 Voltage- 75-93 WNTDNTLGTEITVED 2 3 4 6 2JK4 84.A,85.A,86.A, 5dependent anion- QLAR (SEQ ID 8 9 13 87.A selective channel NO: 906)14 15 protein VDAC1 Voltage- 164-174 VTQSNFAVGYK (SEQ 4 6 8 14 2JK4173.A,174.A, 1, 2 dependent anion- ID NO: 907) 175.A,176.A,selective channel 177.A protein VDAC1 Voltage- 64-74 WTEYGLTFTEK (SEQ2 3 4 6 2JK4 No Overlap — dependent anion- ID NO: 908) 8 9 13selective channel 14 15 protein VDAC1 Voltage- 35-53 SENGLEFTSSGSANTE4 8 9 2JK4 45.A,47.A 7 dependent anion- TTK (SEQ ID NO: 909)selective channel protein VDAC1 Voltage-  175-197 TDEFQLHTNVNDGTE 4 8 142JK4 180.A,181.A, 1, 2, 4 dependent anion- FGGSIYQK(SEQ ID 184.A,185.A,selective channel NO: 910) 186.A,196.A, protein 198.A VDAC1 Voltage-225-236 YQIDPDACFSAK (SEQ 4 8 2JK4 229.A 4 dependent anion- ID NO: 911)selective channel protein VIM Vimentin 176-184 DNLAEDIMR (SEQ ID 6 4YPCNo Overlap — NO: 912) VIM Vimentin 197-207 EEAENTLQSFR (SEQ  2 3 6 94YPC No Overlap — ID NO: 913) 13 14 15 VIM Vimentin 189-196LQEEMLQR (SEQ ID 3 6 4YPC No Overlap — NO: 914) VIM Vimentin 224-235VESLQEEIAFLK (SEQ 4 6 14 4YPC No Overlap — ID NO: 915) VPS33A Vacuolar233-262 NVDLLTPLATQLTYE 14 4BX9 No Overlap — protein sorting-GLIDEIYGIQNSYVK associated protein (SEQ ID NO: 916) 33A XRCC6 X-ray475-488 SDSFENPVLQQHFR 2 3 4 8 1JEY 476.A,486.A, 1, 25 repair cross-(SEQ ID NO: 917) 13 488.A complementing protein 6 XRCC6 X-ray 489-510NLEALALDLMEPEQA 2 3 4 8 1JEY 491.A,497. 14, 25 repair cross-VDLTLPK (SEQ ID 13 A,508.A,50 complementing NO: 176) 9.A protein 6YWHAE 14-3-3 197-215 AAFDDAIAELDTLSEE 13 3UBW 212.A 1 protein epsilonSYK (SEQ ID NO: 92) YWHAE 14-3-3 143-153 EAAENSLVAYK 13 3UBW No Overlap— protein epsilon (SEQ ID NO: 91) YWHAQ 14-3-3 194-212 TAFDEAIAELDTLNED14 5IQP 196.A,197. 2, 6, 10 protein theta SYK A,196.B,197.B,(SEQ ID NO: 93) 209.B,210.B YWHAZ 14-3-3 194-212 TAFDEAIAELDTLSEE 13 145D2D 196.A,197.A, protein zeta/delta SYK 200.A,203.A, (SEQ ID NO: 94)211.A,194.B, 1,6, 13, 19 198.B, 211.B,212.B

TABLE 3 Annotated Estimated SEQ Accension Labeled Functional Distance ID# Protein Name Peptide Peptide Sequence Probes PDB Site from Site NO:P24666 ACP1 Low 42-59 VDSAATSGYEIG 13 3N81 ACT_SITE 2.995 1 molecularNPPDYR 13 13,  weight ACT_SITE phosphotyrosine  19 19,  protein phospACT_SITE 130 130 Q8NI60 ADCK3 277-295 LGQMLSIQDDAFI 14 4PED NP_BIND2.639 2 Chaperone NPHLAK 336 344,  activity of  ACT_SITE bc1  488 488, complex-like,  BINDING mitochondr 358 358 P55263 ADK 209-224IFTLNLSAPFISQF 2 4O1L ACT_SITE 5.239 3 Adenosine YK 317 317,  kinaseMETAL 49 49, METAL 147 147,  METAL 148 148 P30520 ADSS 431-441FIEDELQIPVK 14 2V40 NP_BIND 39 6.392 4 Adenylosuccin 45,  ate synthetaseNP_BIND 67 isozyme 2 69,  NP_BIND 362 364,  NP_BIND 444 447,  ACT_SITE40 40,  ACT_SITE 68 68,  METAL 40 40, METAL 67 67,  BINDING 40 40, BINDING 162 162,  BINDING 176 176,  BINDING 255 255,  BINDING 270 270, BINDING 334 334,  BINDING 336 336 O95831 AIFM1 475-510 PYWHQSMFWSD 3 24LII NP_BIND 0 5 Apoptosis- LGPDVGYEAIGL 4 6 138 142,  inducing VDSSLPTVGVFA NP_BIND factor 1,  K 164 165,  mitochondrial NP_BIND454 455,  BINDING 172 172,  BINDING 177 177,  BINDING 233 233,  BINDING285 285,  BINDING 438 438,  BINDING 483 483 P49419 ALDH7A1 139-162ILVEGVGEVQEY 13 8 4ZUL NP_BIND 4.14 6 Alpha- VDICDYAVGLSR 274 279, aminoadipic ACT_SITE semialdehyde 296 296,  dehydrogenase ACT_SITE330 330,  SITE 195 195 P18085 ARF4 ADP- 39-59 LGEIVTTIPTIGFN 13 3 1Z6XNP_BIND 24 2.742 7 ribosylation 31,  factor 4 NP_BIND 67 VETVEYK 2 871,  NP_BIND 126 129 P84085 ARF5 ADP- 39-59 LGEIVTTIPTIGFN 13 3 2B6HNP_BIND 24 2.639 8 ribosylation VETVEYK 4 2 8 31,  factor 5 NP_BIND 6771,  NP_BIND 126 129 P40616 ARL1 ADP- 163-178 GTGLDEAMEWL 14 13 4DCNNP_BIND 24 3.491 9 ribosylation VETLK 31,  factor-like NP_BIND 45protein 1 48,  NP_BIND 67 71,  NP_BIND 126 129,  NP_BIND 160 161, METAL 31 31, METAL 48 48,  BINDING 70 70 P40616 ARL1 ADP- 37-59LQVGEVVTTIPTI 13 4DCN NP_BIND 24 0 10 ribosylation GFNVETVTYK 31, factor-like NP_BIND 45 48,  NP_BIND 67 71,  NP_BIND 126 129,  NP_BINDprotein 1 160 161,  METAL 31 31, METAL 48 48,  BINDING 70 70 P31939 ATIC178-194 AFTHTAQYDEAI 13 1PKX NP_BIND 12 2.81 11 Bifunctional SDYFR 14, purine NP_BIND 34 biosynthesis NP_BIND 64 protein PURH 67,  NP_BIND101 104,  NP_BIND 125 127,  ACT_SITE 137 137,  ACT_SITE 267 267, BINDING 316 316,  BINDING 339 339,  BINDING 431 431,  BINDING 451 451, BINDING 541 541,  BINDING 588 588,  SITE 266 266 Q13867 BLMH 111-124CYFFLSAFVDTA 14 1CB5 ACT_SITE 15.919 12 Bleomycin QR 73 73,  hydrolaseACT_SITE 372 372,  ACT_SITE 396 396 Q13867 BLMH 203-218 GEISATQDVMME 131CB5 ACT_SITE 19.295 13 Bleomycin EIFR 73 73,  hydrolase ACT_SITE372 372,  ACT_SITE 396 396 P27797 CALR 323-351 SGTIFDNFLITND 13 9 3POWMETAL 26 0 14 Calreticulin EAYAEEFGNETW 6 26, METAL GVTK 62 62, METAL 64 64, METAL 328 328,  BINDING 109 109,  BINDING 111 111,  BINDING128 128,  BINDING 135 135,  BINDING 317 317 P27797 CALR  99-111HEQNEDCGGGYV 6 3POW METAL 26 0 15 Calreticulin K 26, METAL 62 62, METAL 64 64, METAL 328 328,  BINDING 109 109,  BINDING 111 111,  BINDING128 128,  BINDING 135 135,  BINDING 317 317 P07384 CAPN1 175-193LVFVHSAEGNEF 14 2ARY ACT_SITE 7.409 16 Calpain-1 WSALLEK 115 115, catalytic ACT_SITE subunit 272 272,  ACT_SITE 296 296,  SITE 15 16, SITE 27 28 P12277 CKB Creatine 14-32 FPAEDEFPDLSAH 3 3B6R NP_BIND 2.79717 kinase B-type NNHMAK 128 132,  NP_BIND 320 325,  BINDING 72 72, BINDING 130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232, BINDING 236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320, BINDING 335 335 P12277 CKB Creatine 157-172 LAVEALSSLDGD 13 3B6R NP_BIND7.719 18 kmase B-type LAGR 128 132,  NP_BIND 320 325,  BINDING 72 72, BINDING 130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232, BINDING 236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320, BINDING 335 335 P12277 CKB Creatine 224-236 TFLVWVNEEDHL 3 3B6R NP_BIND0 19 kinase B-type R 128 132,  NP_BIND 320 325,  BINDING 72 72,  BINDING130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232,  BINDING236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320,  BINDING335 335 P12277 CKB Creatine 253-265 FCTGLTQIETLFK 13 3B6R NP_BIND 3.56920 kmase B-type 128 132,  NP_BIND 320 325,  BINDING 72 72,  BINDING130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232,  BINDING236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320,  BINDING335 335 P12277 CKB Creatine 342-358 LGFSEVELVQMV 3 13 3B6R NP_BIND 4.63221 kinase B-type VDGVK 128 132,  NP_BIND 320 325,  BINDING 72 72, BINDING 130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232, BINDING 236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320, BINDING 335 335 P12277 CKB Creatine 367-381 LEQGQAIDDLMP 13 3B6R NP_BIND15.156 22 kinase B-type AQK 128 132,  NP_BIND 320 325,  BINDING 72 72, BINDING 130 130,  BINDING 132 132,  BINDING 191 191,  BINDING 232 232, BINDING 236 236,  BINDING 285 285,  BINDING 292 292,  BINDING 320 320, BINDING 335 335 P12532 CKMT1B 257-269 SFLIWVNEEDHT 3 1QK1 NP_BIND 0 2Creatine kinase R 161 165,  U-type,  NP_BIND mitochondrial 353 358, BINDING 224 224,  BINDING 269 269,  BINDING 325 325,  BINDING 368 368Q16740 CLPP Putative 215-226 QSLQVIESAMER 6 1TG6 ACT_SITE 3.045 24 ATP-153 153,  dependent Clp ACT_SITE protease 178 178 proteolytic su P48729CSNK1A1 84-106 DYNVLVMDLLG 14 5FQD NP_BIND 23 2.833 25 Casein kinase IPSLEDLFNFCSR 31,  isoform alpha ACT_SITE 136 136,  BINDING 46 46 P67870CSNK2B 112-134 VYCENQPMLPIG 14 4NH1 METAL 109 0 26 Casein kinaseLSDIPGEAMVK 109, METAL II subunit beta 114 114,  METAL 137 137, METAL140 140 P07858 CTSB 315-331 GQDHCGIESEVV 13 4 3K9M ACT_SITE 6.662 27Cathepsin B AGIPR 2 9 108 108,  ACT_SITE 278 278,  ACT_SITE 298 298P07339 CTSD 236-253 DPDAQPGGELML 9 4OD9 ACT_SITE 11.321 28 Cathepsin DGGTDSK 97 97,  ACT_SITE 295 295 P07339 CTSD 288-309 EGCEAIVDTGTSL 13 144OD9 ACT_SITE 0 29 Cathepsin D MVGPVDEVR 15 4  97 97,  6 9 8 ACT SITE295 295 P07339 CTSD 314-331 AIGAVPLIQGEY 14 15 4OD9 ACT_SITE 13.281 30Cathepsin D MIPCEK 3 2 4 97 97,  13 6 ACT_SITE 9 8 295 295 P00387 CYB5R3235-241 LWYTLDR 3 1UMK NP_BIND 2.96 31 NADH- 132 147,  cytochrome b5NP_BIND reductase 3 171 206 Q16698 DECR1 2,4- 299-315 FDGGEEVLISGEF 61W6U NP_BIND 66 2.779 32 dienoyl-CoA NDLR 71,  reductase,  NP_BINDmitochondrial 240 243,  ACT_SITE 199 199,  BINDING 91 91,  BINDING 9191,  BINDING 117 117,  BINDING 119 119,  BINDING 149 149,  BINDING157 157,  BINDING 214 214,  BINDING 251 251 Q08211 DHX9 ATP- 448-456ISAVSVAER 3 3LLM NP_BIND 3.525 33 dependent 411 419 RNA helicase AP09622 DLD 450-482 VLGAHILGPGAG 14 4 3RNM NP_BIND 71 6.842 34Dihydrolipoyl EMVNEAALALEY 13 80,  dehydrogenase,  GASCEDIAR NP_BINDmitochondrial 183 185,  NP_BIND 220 227,  NP_BIND 361 364,  ACT_SITE487 487,  BINDING 89 89,  BINDING 154 154,  BINDING 243 243,  BINDING278 278,  BINDING 314 314,  BINDING 355 355 Q13011 ECH1 113-131MFTAGIDLMDM 6 2VRE BINDING 3.9 35 Delta(3,5)- ASDILQPK 174 174, Delta(2,4)- SITE 197 dienoyl-CoA 197, SITE isomerase,  205 205 mitocQ13011 ECH1 149-158 YQETFNVIER 6 2VRE BINDING 2.823 36 Delta(3,5)-174 174,  Delta(2,4)- SITE 197 dienoyl-CoA 197, SITE isomerase,  205 205mitoc Q13011 ECH1 197-211 EVDVGLAADVG 13 14 2VRE BINDING 0 37Delta(3,5)- TLQR 15 3 174 174,  Delta(2,4)- 4 6 8 SITE 197 dienoyl-CoA197, SITE isomerase,  205 205 mitoc P60842 EIF4A1 178-190 MFVLDEADEMLS13 2ZU6 NP_BIND 76 2.797 38 Eukaryotic R 83 initiation factor 4A-IP60842 EIF4A1 69-82 GYDVIAQAQSGT 14 13 2ZU NP_BIND 76 0 39 Eukaryotic GK9 6 83 initiation factor 4A-I Q14240 EIF4A2 Eukaryotic 70-83GYDVIAQAQSGT 13 3B0R NP_BIND 77 0 40 initiation factor GK 84 4A-IIP38117 ETFB Electron 36-51 HSMNPFCEIAVEE 3 2A1T BINDING 16 5.189 41transfer AVR 16 flavoprotein subunit beta P22830 FECH 254-272SEVVILFSAHSLP 4 3HCN ACT_SITE 3.373 42 Fen-ochelatase,  MSVVNR 230 230, mitochondrial ACT_SITE 383 383,  METAL 196 196, METAL 403 403, METAL 406 406, METAL 411 411 P06280 GLA Alpha- 241-252 SILDWTSFNQER 9355Z ACT_SITE 5.4 43 galactosidase 170 170,  A AC_SITE 231 231 P06280GLA Alpha- 50-67 FMCNLDCQEEPD 9 3S5Z ACT_SITE 8.622 44 galactosidaseSCISEK 170 170,  A ACT_SITE 231 231 P06280 GLA Alpha- 68-82 LFMEMAELMVSE4 355Z ACT_SITE 14.579 45 galactosidase GWK 170 170,  A ACT_SITE 231 231P16278 GLB1 Beta- 286-299 TEAVASSLYDILA 9 3THC ACT_SITE 7.48 46galactosidase R 188 188,  ACT_SITE 268 268 Q04760 GLO1 160-179GLAFIQDPDGYW 14 3 3W0T ACT_SITE 0 47 Lactoyl- IEILNPNK 173 173, glutathione- METAL 34 lyase 34, METAL 100 100,  METAL 127 127, METAL173 173,  BINDING 34 34,  BINDING 38 38,  BINDING 104 104,  BINDING123 123,  BINDING 127 127 P00367 GLUD1 152-162 YSTDVSVDEVK 6 1L1FNP_BIND 3.908 48 Glutamate 141 143,  dehydrogenase ACT_SITE 1, 183 183,  mitochondrial BINDING 147 147,  BINDING 171 171,  BINDING176 176,  BINDING 252 252,  BINDING 266 266,  BINDING 270 270,  BINDING319 319,  BINDING 322 322,  BINDING 438 438,  BINDING 444 444,  BINDING450 450,  BINDING 516 516 P00367 GLUD1 481-496 HGGTIPIVPTAEF 6 1L1FNP_BIND 10.438 49 Glutamate QDR 141 143,  dehydrogenase ACT_SITE 1, 183 183,  mitochondrial BINDING 147 147,  BINDING 171 171,  BINDING176 176,  BINDING 252 252,  BINDING 266 266,  BINDING 270 270,  BINDING319 319,  BINDING 322 322,  BINDING 438 438,  BINDING 444 444,  BINDING450 450,  BINDING 516 516 Q9H4A6 GOLPH3 75-90 EGYTSFWNDCISS 14 3KN1BINDING 81 0 50 Golgi GLR 81,  phosphoprotein BINDING 90 3 90,  BINDING171 171,  BINDING 174 174 P09211 GSTP1 56-71 FQDGDLTLYQSN 2 2A2RBINDING 8 3.198 51 Glutathione S- TILR 8, BINDING transferase P 14 14, BINDING 39 39,  BINDING 45 45 P69905 HBA2 18-32 VGAHAGEYGAE 4 4X0LMETAL 59 3.717 52 Hemoglobin ALER 59, METAL subunit alpha 88 88, SITE12 12, SITE 57 57, SITE 61 61, SITE 91 91, SITE 100 100 P69905 HBA2 94-100 VDPVNFK 4 4X0L METAL 59 0 53 Hemoglobin 59, METAL subunit alpha88 88, SITE 12 12, SITE 57 57, SITE 61 61, SITE 91 91, SITE 100 100P06865 HEXA Beta- 489-499 LTSDLTFAYER 9 2GJX ACT_SITE 28.463 54hexosaminidase 323 323 subunit alpha P30519 HMOX2 Heme 48-55 AENTQFVK15 14 4WMB METAL 45 3.21 55 oxygenase 2 3 4 2 45 6 8 P30519 HMOX2 Heme69-87 LATTALYFTYSA 14 4WMH METAL 45 11.935 56 oxygenase 2 LEEEMER 45P51659 HSD17B4 169-183 LGLLGLANSLAIE 3 1ZBQ NP_BIND 13 1.327 57multifunctional GR 37,  enzyme type 2 NP_BIND 75 76,  NP_BIND 164 168, NP_BIND 196 199,  ACT_SITE 164 164,  BINDING 21 21,  BINDING 40 40, BINDING 99 99,  BINDING 151 151,  BINDING 435 435,  BINDING 533 533, BINDING 563 563,  BINDING 706 706,  BINDING 724 724 P08238 HSP90AB1  360-378 VFIMDSCDELIPE 14 13 3PRY BINDING 46 12.676 58 Heat shock YLNFIR46,  protein HSP BINDING 88 90-beta 88,  BINDING 107 107,  BINDING133 133,  BINDING 392 392 P08238 HSP90AB1  507-526 GFEVVYMTEPID 13 143PRY BINDING 46 35.151 59 Heat shock EYCVQQLK 46,  protein HSPBINDING 88 90-beta 88,  BINDING 107 107,  BINDING 133 133,  BINDING392 392 P14625 HSP90B1 117-135 LISLTDENALSGN 9 4NH9 BINDING 3.486 60Endoplasmin EELTVK 107 107,  BINDING 149 149,  BINDING 162 162,  BINDING168 168,  BINDING 199 199,  BINDING 448 448 P14625 HSP90B1 271-285YSQFINFPIYVWS 6 4NH9 BINDING 7.026 61 Endoplasmin SK 107 107,  BINDING149 149,  BINDING 162 162,  BINDING 168 168,  BINDING 199 199,  BINDING448 448 P11142 HSPA8 Heat 113-126 SFYPEEVSSMVLT 13 14 3LDQ NP_BIND 124.637 62 shock cognate K 15,  71 kDa protein NP_BIND 202 204,  NP_BIND268 275,  NP_BIND 339 342,  BINDING 71 71 P12268 IMPDH2 110-124YEQGFITDPVVLS 13 1NF7 NP_BIND 21.6 63 Inosine-5- PK 274 276, monophosphate NP_BIND dehydrogenase 324 326,  2 ACT_SITE 331 331, ACT_SITE 429 429,  METAL 326 326, METAL 328 328,  METAL 331 331, METAL500 500,  METAL 501 501, METAL 502 502,  BINDING 329 329,  BINDING441 441 P00338 LDHA L-  43-57 DLADELALVDVI 9 4JNK NP_BIND 29 0 64lactate EDK 57,  dehydrogenase ACT_SITE A chain 193 193,  BINDING 99 99,BINDING 106 106,  BINDING 138 138,  BINDING 169 169,  BINDING 248 248P07195 LDHB L- 234-244 MVVESAYEVEK 4 1I0Z NP_BIND 31 3.118 65 lactate53,  dehydrogenase ACT_SITE B chain 194 194,  BINDING 100 100,  BINDING107 107,  BINDING 139 139,  BINDING 170 170,  BINDING 249 249 Q99538LGMN 102-118 DYTGEDVTPQNF 9 4N6O ACT_SITE 10.316 66 Legumain LAVLR148 148,  ACT_SITE 189 189,  SITE 323 324 P09960 LTA4H 366-386LVVDLTDIDPDV 13 4 3U9W ACT_SITE 0 67 Leukotriene A- AYSSVPYEK 8297 297,  4 hydrolase ACT_SITE 384 384,  METAL 296 296, METAL 300 300, METAL 319 319, SITE 376 376,  SITE 379 379 P43490 NAMPT 175-189YLLETSGNLDGL 13 14 4LVF BINDING 9.786 68 Nicotinamide EYK 15 3 196 196, phosphoribosyl 6 8 BINDING transferase 219 219,  BINDING 247 247, BINDING 311 311,  BINDING 384 384,  BINDING 392 392 P06748 NPM1 55-73DELHIVEAEAMN 13 2P1B SITE 55 55,  0 69 Nucleophosmin YEGSPIKSITE 80 80,  SITE 175 176 P06748 NPM1  81-101 MSVQPTVSLGGF 13 2P1BSITE 55 55,  1.327 70 Nucleophosmin EITPPVVLR SITE 80 80,  SITE 175 176P22061 PCMT1 179-197 LILPVGPAGGNQ 14 3 1I1N ACT_SITE 8.729 71 Protein-L-MLEQYDK 2 60 60 isoaspartate(D- aspartate) O- methyhransf P11177 PDHB53-68 VFLLGEEVAQYD 13 14 3EXE BINDING 89 2.492 72 Pyruvate GAYK 3 2 89dehydrogenase E1 component subunit beta,  P00558 PGK1 333-350QIVWNGPVGVFE 3 2WZB NP_BIND 0 73 Phosphoglycerate WEAFAR 373 376, kinase 1 BINDING 39 39,  BINDING 123 123,  BINDING 171 171,  BINDING220 220,  BINDING 313 313,  BINDING 344 344 P14618 PKM Pyruyate 174-186IYVDDGLISLQVK 2 9  4FXF NP_BIND 75 3.318 74 kinase 78, METAL isozymes75 75,  M1/M2 METAL 77 77, METAL 113 113,  METAL 114 114, METAL272 272,  METAL 296 296,  BINDING 70 70,  BINDING 73 73,  BINDING106 106,  BINDING 120 120,  BINDING 207 207,  BINDING 270 270,  BINDING295 295,  BINDING 296 296,  BINDING 328 328,  BINDING 464 464,  BINDING482 482,  BINDING 489 489,  SITE 270 270, SITE 433 433 P14618PKM Pyruvate 401-422 LAPITSDPTEATA 2 9 4FXF NP_BIND 75 9.657 75 kinaseVGAVEASFK 78, METAL isozymes 75 75,  M1/M2 METAL 77 77, METAL 113 113, METAL 114 114, METAL 272 272,  METAL 296 296,  BINDING 70 70, BINDING 73 73,  BINDING 106 106,  BINDING 120 120,  BINDING 207 207, BINDING 270 270,  BINDING 295 295,  BINDING 296 296,  BINDING 328 328, BINDING 464 464,  BINDING 482 482,  BINDING 489 489,  SITE 270 270, SITE433 433 P16435 POR NADPH-- 369-382 TALTYYLDITNPP 13 14 3QFS NP_BIND 863.068 76 cytochrome R 91,  P450 reductase NP_BIND 138 141,  NP_BIND173 182,  NP_BIND 454 457,  NP_BIND 472 474,  NP_BIND 488 491,  NP_BIND596 597,  NP_BIND 602 606,  BINDING 208 208,  BINDING 298 298,  BINDING424 424,  BINDING 478 478,  BINDING 535 535,  BINDING 638 638,  BINDING676 676 P62136 PPP1CA 133-141 IYGFYDECK 2 4XPN ACT_SITE 4.098 77 Serine/125 125,  threonine- METAL 64 protein 64, METAL phosphatase 66 66, PP1-alpha cat METAL 92 92, METAL 92 92,  METAL 92 92, METAL 124 124, METAL 124 124, METAL 173 173,  METAL 173 173, METAL 248 248,  METAL 248248 P36873 PPP1CC 133-141 IYGFYDECK 2  4UT2 ACT_SITE 4.153 78 Serine/125 125,  threonine- METAL 64 protein 64, METAL phosphatase 66 66, PP1-gamma METAL 92 cat 92, METAL 92 92,  METAL 124 124, METAL 173 173, METAL 248 248, SITE 273 273 P36873 PPP1CC 44-60 EIFLSQPILLELEA 14 4UT2ACT_SITE 10.048 79 Serine/ PLK 125 125,  threonine- METAL 64 protein64, METAL phosphatase 66 66,  PP1-gamma METAL 92 cat 92, METAL 92 92, METAL 124 124, METAL 173 173,  METAL 248 248, SITE 273 273 P50897 PPT1 75-101 TLMEDVENSFFL 13 14 3GRO ACT_SITE 9.259 80 Palmitoyl-NVNSQVTTVCQA 15 4 115 115,  protein LAK 2 9 8 ACT_SITE thioesterase 1233 233,  ACT_SITE 289 289 P32119 PRDX2 120-127 TDEGIAYR 13 1QMVACT_SITE 2.624 81 Peroxiredoxin- 51 51 2 P28070 PSMB4 61-80 FEGGVVIAADML6 4R3O ACT_SITE 11.396 82 Proteasome GSYGSLAR 46 46 subunit beta type-4P28074 PSMB5 141-150 LLANMVYQYK 4 3 4R3O ACT_SITE 10.794 83 Proteasome 660 60,  subunit beta BINDING type-5 108 108 P28074 PSMB5 226-239DAYSGGAVNLY 6 4R3O ACT_SITE 2.795 84 Proteasome HVR 60 60,  subunit betaBINDING type-5 108 108 P28072 PSMB6  80-118 SGSAADTQAVAD 14 3 4R3OACT_SITE 3.784 85 Proteasome AVTYQLGFHSIEL 6 35 35 subunit betaNEPPLVHTAASLF type-6 K P51149 RAB7A Ras- 104-113 DEFLIQASPR 14 1YHNNP_BIND 15 8.675 86 related protein 22,  Rab-7a NP_BIND 34 40, NP_BIND 63 67,  NP_BIND 125 128,  NP_BIND 156 157 Q9Y230 RUVBL2 315-330ALESDMAPVLIM 14 3UK6 NP_BIND 77 3.038 87 RuyB-like 2 ATNR 84 Q9H7B4SMYD3 SET 255-265 DQYCLECDCFR 9 5HQ8 BINDING 0 88 and MYND 124 124, domain- BINDING containing 132 132,  protein 3 BINDING 181 181,  BINDING239 239,  BINDING 259 259 O14773 TPP1 521-558 GCHESCLDEEVE 13 14 3EDYACT_SITE 0 89 Tripeptidyl- GQGFCSGPGWDP 15 4 272 272,  peptidase 1VTGWGTPNFPAL 9 ACT_SITE LK 276 276,  ACT_SITE 475 475,  METAL 517517, METAL 518 518,  METAL 539 539, METAL 541 541,  METAL 543 543 Q9BRA2TXNDC17 42477 YEEVSVSGFEEFH 14 IWOU ACT_SITE 12.278 90 Thioredoxin R43 43,  domain- ACT_SITE containing 46 46, SITE protein 17 44 44, SITE45 45 P62258 YWHAE 14-3- 143-153 EAAENSLVAYK 13 3UBW SITE 57 57,  2.85191 3 protein SITE 130 130 epsilon P62258 YWHAE 14-3- 197-215AAFDDAIAELDT 13 3UBW SITE 57 57,  14.177 92 3 protein LSEESYKSITE 130 130 epsilon P27348 YWHAQ 14-3- 194-212 TAFDEAIAELDTL 14 5IQPSITE 56 56,  14.319 93 3 protein theta NEDSYK SITE 127 127 P63104YWHAZ 14-3- 194-212 TAFDEAIAELDTL 14 13 5D2D SITE 56 56,  14.87 943 protein SEESYK SITE 127 127 zeta/delta Q9UQ84 EX01 139-160SQGVDCLVAPYE 13 2 3QEB METAL 30 0 95 Exonuclease 1 ADAQLAYLNK 6 9 830, METAL 78 78,  METAL 150 150, METAL 152 152,  METAL 171 171, METAL173 173,  METAL 225 225 P02545 LMNA 352-366 MQQQLDEYQELL 13 6 3V5BSITE 266 28.999 96 Prelamin-A/C DIK SITE 330 266, SITE 325 325, 330, SITE 646 647

Table 4 illustrates exemplary list of proteins identified by a methoddescribed herein.

Accession # Protein Name P01023 A2M Alpha-2-macroglobulin Q9NRG9 AAASAladin Q13685 AAMP Angio-associated migratory cell protein P49588 AARSAlanine--tRNA ligase, cytoplasmic Q5JTZ9 AARS2 Alanine--tRNA ligase,mitochondrial Q9NRN7 AASDHPPT L-aminoadipate- semialdehydedehydrogenase-phosphop P08183 ABCB1 Multidrug resistance protein 1Q9NRK6 ABCB10 ATP-binding cassette sub-family B member 10, mitoc O75027ABCB7 ATP-binding cassette sub-family B member 7, mitoch Q9NUT2 ABCB8ATP-binding cassette sub-family B member 8, mitoch P28288 ABCD3ATP-binding cassette sub-family D member 3 P61221 ABCE1 ATP-bindingcassette sub-family E member 1 Q8NE71 ABCF1 ATP-binding cassettesub-family F member 1 Q9UG63 ABCF2 ATP-binding cassette sub-family Fmember 2 Q9NUJ1 ABHD10 Abhydrolase domain-containing protein 10,mitochon Q8N2K0 ABHD12 Monoacylglycerol lipase ABHD12 O95870 ABHD16AAbhydrolase domain- containing protein 16A P09110 ACAA1 3-ketoacyl-CoAthiolase, peroxisomal Q9H845 ACAD9 Acyl-CoA dehydrogenase family member9, mitochondr P11310 ACADM Medium-chain specific acyl-CoA dehydrogenase,mito P45954 ACADSB Short/branched chain specific acyl-CoA dehydrogenaP49748 ACADVL Very long-chain specific acyl- CoA dehydrogenase, m P24752ACAT1 Acetyl-CoA acetyltransferase, mitochondrial Q9BWD1 ACAT2Acetyl-CoA acetyltransferase, cytosolic Q9H3P7 ACBD3 Golgi residentprotein GCP60 Q9UKV3 ACIN1 Apoptotic chromatin condensation inducer inthe nu P53396 ACLY ATP-citrate synthase Q99798 ACO2 Aconitate hydratase,mitochondrial P49753 ACOT2 Acyl-coenzyme A thioesterase 2, mitochondrialO00154 ACOT7 Cytosolic acyl coenzyme A thioester hydrolase Q9Y305 ACOT9Acyl-coenzyme A thioesterase 9, mitochondrial Q15067 ACOX1 Peroxisomalacyl-coenzyme A oxidase 1 P24666 ACP1 Low molecular weightphosphotyrosine protein phosp P11117 ACP2 Lysosomal acid phosphataseQ9NPH0 ACP6 Lysophosphatidic acid phosphatase type 6 P33121 ACSL1Long-chain-fatty-acid--CoA ligase 1 O95573 ACSL3Long-chain-fatty-acid--CoA ligase 3 O60488 ACSL4Long-chain-fatty-acid--CoA ligase 4 Q53FZ2 ACSM3 Acyl-coenzyme Asynthetase ACSM3, mitochondrial P68133 ACTA1 Actin, alpha skeletalmuscle P62736 ACTA2 Actin, aortic smooth muscle P60709 ACTB Actin,cytoplasmic 1 Q562R1 ACTBL2 Beta-actin-like protein 2 P68032 ACTC1Actin, alpha cardiac muscle 1 P63261 ACTG1 Actin, cytoplasmic 2 O96019ACTL6A Actin-like protein 6A P12814 ACTN1 Alpha-actinin-1 Q08043 ACTN3Alpha-actinin-3 O43707 ACTN4 Alpha-actinin-4 P61163 ACTR1AAlpha-centractin P61160 ACTR2 Actin-related protein 2 P61158 ACTR3Actin-related protein 3 P55265 ADAR Double-stranded RNA-specificadenosine deaminase Q8NI60 ADCK3 Chaperone activity of bc1 complex-like,mitochondr Q96D53 ADCK4 Uncharacterized aarF domain- containing proteinkin P35611 ADD1 Alpha-adducin P55263 ADK Adenosine kinase Q9BRR6 ADPGKADP-dependent glucokinase P30520 ADSS Adenylosuccinate synthetaseisozyme 2 Q9Y4W6 AFG3L2 AFG3-like protein 2 Q53H12 AGK Acylglycerolkinase, mitochondrial P35573 AGL Glycogen debranching enzyme Q99943AGPAT1 1-acyl-sn-glycerol-3-phosphate acyltransferase alp Q9NUQ2 AGPAT51-acyl-sn-glycerol-3-phosphate acyltransferase eps Q86UL3 AGPAT6Glycerol-3-phosphate acyltransferase 4 O00116 AGPSAlkyldihydroxyacetonephosphate synthase, peroxisom P23526 AHCYAdenosylhomocysteinase O43865 AHCYL1 Putative adenosylhomocysteinase 2Q96HN2 AHCYL2 Putative adenosylhomocysteinase 3 O95433 AHSA1 Activatorof 90 kDa heat shock protein ATPase homo O95831 AIFM1 Apoptosis-inducingfactor 1, mitochondrial Q12904 AIMP1 Aminoacyl tRNA synthasecomplex-interacting multif Q13155 AIMP2 Aminoacyl tRNA synthasecomplex-interacting multif O00170 AIP AH receptor-interacting proteinP54819 AK2 Adenylate kinase 2, mitochondrial Q92667 AKAP1 A-kinaseanchor protein 1, mitochondrial Q02952 AKAP12 A-kinase anchor protein 12O43823 AKAP8 A-kinase anchor protein 8 Q9ULX6 AKAP8L A-kinase anchorprotein 8-like Q04828 AKR1C1 Aldo-keto reductase family 1 member C1P31751 AKT2 RAC-beta serine/threonine-protein kinase P54886 ALDH18A1Delta-1-pyrroline-5- carboxylate synthase P00352 ALDH1A1 Retinaldehydrogenase 1 P30837 ALDH1B1 Aldehyde dehydrogenase X, mitochondrialQ3SY69 ALDH1L2 Mitochondrial 10- formyltetrahydrofolate dehydrogenP05091 ALDH2 Aldehyde dehydrogenase, mitochondrial P51648 ALDH3A2 Fattyaldehyde dehydrogenase Q02252 ALDH6A1 Methylmalonate-semialdehydedehydrogenase [acylati P49419 ALDH7A1 Alpha-aminoadipic semialdehydedehydrogenase P49189 ALDH9A1 4-trimethylaminobutyraldehyde dehydrogenaseQ9BT22 ALG1 Chitobiosyldiphosphodolichol beta- mannosyltransfer Q9BV10ALG12 Dol-P-Man:Man(7)GlcNAc(2)-PP- Dol alpha-1,6-mannosy Q9Y673 ALG5Dolichyl-phosphate beta- glucosyltransferase Q9Y672 ALG6 Dolichylpyrophosphate Man9GlcNAc2 alpha-1,3-gluco Q86V81 ALYREF THO complexsubunit 4 Q9UJX4 ANAPC5 Anaphase-promoting complex subunit 5 Q9UJX3ANAPC7 Anaphase-promoting complex subunit 7 Q86XL3 ANKLE2 Ankyrin repeatand LEM domain-containing protein 2 Q8IZ07 ANKRD13A Ankyin repeatdomain- containing protein 13A Q9NW15 ANO10 Anoctamin-10 P39687 ANP32AAcidic leucine-rich nuclear phosphoprotein 32 fami Q92688 ANP32B Acidicleucine-rich nuclear phosphoprotein 32 fami Q9BTT0 ANP32E Acidicleucine-rich nuclear phosphoprotein 32 fami P04083 ANXA1 Annexin A1P50995 ANXA11 Annexin A11 P07355 ANXA2 Annexin A2 P08758 ANXA5 AnnexinA5 P08133 ANXA6 Annexin A6 P20073 ANXA7 Annexin A7 Q10567 AP1B1 AP-1complex subunit beta-1 P63010 AP2B1 AP-2 complex subunit beta Q96CW1AP2M1 AP-2 complex subunit mu O00203 AP3B1 AP-3 complex subunit beta-1O14617 AP3D1 AP-3 complex subunit delta-1 Q9Y2T2 AP3M1 AP-3 complexsubunit mu-1 P13798 APEH Acylamino-acid-releasing enzyme Q9BZZ5 API5Apoptosis inhibitor 5 Q06481 APLP2 Amyloid-like protein 2 Q9HDC9 APMAPAdipocyte plasma membrane- associated protein Q8NCW5 APOA1BPNAD(P)H-hydrate epimerase Q9UH17 APOBEC3B Probable DNA dC-dU- editingenzyme APOBEC-3B P02649 APOE Apolipoprotein E Q9BQE5 APOL2Apolipoprotein L2 Q9BUR5 APOO Apolipoprotein O Q6UXV4 APOOLApolipoprotein O-like P05067 APP Amyloid beta A4 protein P07741 APRTAdenine phosphoribosyltransferase P10398 ARAF Serine/threonine-proteinkinase A- Raf P48444 ARCN1 Coatomer subunit delta P84077 ARF1ADP-ribosylation factor 1 P61204 ARF3 ADP-ribosylation factor 3 P18085ARF4 ADP-ribosylation factor 4 P84085 ARF5 ADP-ribosylation factor 5E7EV62 ARFGAP1 ADP-ribosylation factor GTPase-activating protein Q8N6H7ARFGAP2 ADP-ribosylation factor GTPase-activating protein P53367 ARFIP1Arfaptin-1 Q92888 ARHGEF1 Rho guanine nucleotide exchange factor 1Q92974 ARHGEF2 Rho guanine nucleotide exchange factor 2 O14497 ARID1AAT-rich interactive domain- containing protein 1A P40616 ARL1ADP-ribosylation factor-like protein 1 Q8N6S5 ARL6IP6 ADP-ribosylationfactor-like protein 6-interacting Q9NVJ2 ARL8B ADP-ribosylationfactor-like protein 8B Q9NVT9 ARMC1 Armadillo repeat-containing protein1 Q8N2F6 ARMC10 Armadillo repeat-containing protein 10 Q9UH62 ARMCX3Armadillo repeat-containing X- linked protein 3 Q13510 ASAH1 Acidceramidase Q9UBL3 ASH2L Set1/Ash2 histone methyltransferase complexsubuni O43681 ASNA1 ATPase ASNA1 P08243 ASNS Asparagine synthetase[glutamine- hydrolyzing] Q12797 ASPH Aspartyl/asparaginyl beta-hydroxylase Q8NBU5 ATAD1 ATPase family AAA domain- containing protein 1Q9NVI7 ATAD3A ATPase family AAA domain- containing protein 3A Q5T9A4ATAD3B ATPase family AAA domain- containing protein 3B Q5T2N8 ATAD3CATPase family AAA domain- containing protein 3C Q7Z3C6 ATG9AAutophagy-related protein 9A P31939 ATIC Bifunctional purinebiosynthesis protein PURH Q8NHH9 ATL2 Atlastin-2 Q6DD88 ATL3 Atlastin-3Q9HD20 ATP13A1 Probable cation-transporting ATPase 13A1 P05023 ATP1A1Sodium/potassium-transporting ATPase subunit alpha P13637 ATP1A3Sodium/potassium-transporting ATPase subunit alpha P54709 ATP1B3Sodium/potassium-transporting ATPase subunit beta- P16615 ATP2A2Sarcoplasmic/endoplasmic reticulum calcium ATPase Q93084 ATP2A3Sarcoplasmic/endoplasmic reticulum calcium ATPase P20020 ATP2B1 Plasmamembrane calcium- transporting ATPase 1 P23634 ATP2B4 Plasma membranecalcium- transporting ATPase 4 P25705 ATP5A1 ATP synthase subunit alpha,mitochondrial P06576 ATP5B ATP synthase subunit beta, mitochondrialP36542 ATP5C1 ATP synthase subunit gamma, mitochondrial P24539 ATP5F1ATP synthase subunit b, mitochondrial O75947 ATP5H ATP synthase subunitd, mitochondrial O75964 ATP5L ATP synthase subunit g, mitochondrialP48047 ATP5O ATP synthase subunit O, mitochondrial Q93050 ATP6V0A1V-type proton ATPase 116 kDa subunit a isoform 1 Q9Y487 ATP6V0A2 V-typeproton ATPase 116 kDa subunit a isoform 2 P61421 ATP6V0D1 V-type protonATPase subunit d 1 P38606 ATP6V1A V-type proton ATPase catalytic subunitA P21281 ATP6V1B2 V-type proton ATPase subunit B, brain isoform P36543ATP6V1E1 V-type proton ATPase subunit E 1 Q9UBB4 ATXN10 Ataxin-10 Q99700ATXN2 Ataxin-2 Q8WWM7 ATXN2L Ataxin-2-like protein Q9Y679 AUP1 Ancientubiquitous protein 1 O14965 AURKA Aurora kinase A O43505 B3GNT1N-acetyllactosaminide beta-1,3- N-acetylglucosaminy O95817 BAG3 BAGfamily molecular chaperone regulator 3 O95429 BAG4 BAG family molecularchaperone regulator 4 Q9UL15 BAG5 BAG family molecular chaperoneregulator 5 P46379 BAG6 Large proline-rich protein BAG6 Q9UQB8 BAIAP2Brain-specific angiogenesis inhibitor 1-associated B0UX83 BAT3 HLA-Bassociated transcript 3 B0UXB6 BAT5 Abhydrolase domain-containingprotein 16A Q07812 BAX Apoptosis regulator BAX Q9NRL2 BAZ1A Bromodomainadjacent to zinc finger domain protein Q9UIG0 BAZ1B Tyrosine-proteinkinase BAZ1B P51572 BCAP31 B-cell receptor-associated protein 31 O75934BCAS2 Pre-mRNA-splicing factor SPF27 Q9P287 BCCIP BRCA2 andCDKN1A-interacting protein P12694 BCKDHA 2-oxoisovalerate dehydrogenasesubunit alpha, mito Q9BXK5 BCL2L13 Bcl-2-like protein 13 Q9NYF8 BCLAF1Bcl-2-associated transcription factor 1 Q9Y276 BCS1L Mitochondrialchaperone BCS1 P55957 BID BH3-interacting domain death agonist Q13867BLMH Bleomycin hydrolase P53004 BLVRA Biliverdin reductase A P30043BLVRB Flavin reductase (NADPH) Q9NSY1 BMP2K BMP-2-inducible proteinkinase Q14137 BOP1 Ribosome biogenesis protein BOP1 Q6PJG6 BRAT1BRCA1-associated ATM activator 1 P25440 BRD2 Bromodomain-containingprotein 2 Q8WY22 BRI3BP BRI3-binding protein Q8TDN6 BRIX1 Ribosomebiogenesis protein BRX1 homolog Q5VW32 BROX BRO1 domain-containingprotein BROX Q9NW68 BSDC1 BSD domain-containing protein 1 P35613 BSGBasigin Q06187 BTK Tyrosine-protein kinase BTK O60566 BUB1B Mitoticcheckpoint serine/threonine-protein kinase O43684 BUB3 Mitoticcheckpoint protein BUB3 Q13895 BYSL Bystin Q7L1Q6 BZW1 Basic leucinezipper and W2 domain-containing prot Q69YU5 C12orf73 Uncharacterizedprotein C12orf73 Q9Y224 C14orf166 UPF0568 protein C14orf166 Q96GQ5C16orf58 UPF0420 protein C16orf58 Q9BSF4 C19orf52 Uncharacterizedprotein C19orf52 Q4ZIN3 C19orf6 Membralin E9PFR7 C1orf27 Protein C1orf27Q07021 C1QBP Complement component 1 Q subcomponent-binding prot Q9BQP7C20orf72 Uncharacterized protein C20orf72 P30042 C21orf33 ES1 proteinhomolog, mitochondrial Q9H6V9 C2orf43 UPF0554 protein C2orf43 Q8WWC4C2orf47 Uncharacterized protein C2orf47, mitochondrial Q96FZ2 C3orf37UPF0361 protein C3orf37 Q9H993 C6orf211 UPF0364 protein C6orf211 Q9H7E9C8orf33 UPF0488 protein C8orf33 Q5T6V5 C9orf64 UPF0553 protein C9orf64Q9Y376 CAB39 Calcium-binding protein 39 Q9HB71 CACYBP Calcyclin-bindingprotein P27708 CAD CAD protein Q9BY67 CADM1 Cell adhesion molecule 1P05937 CALB1 Calbindin P62158 CALM1 Calmodulin P27797 CALR CalreticulinO43852 CALU Calumenin Q14012 CAMK1 Calcium/calmodulin-dependent proteinkinase type 1 Q13557 CAMK2D Calcium/calmodulin-dependent protein kinasetype I Q13555 CAMK2G Calcium/calmodulin-dependent protein kinase type IP27824 CANX Calnexin P07384 CAPN1 Calpain-1 catalytic subunit P17655CAPN2 Calpain-2 catalytic subunit P04632 CAPNS1 Calpain small subunit 1Q14444 CAPRIN1 Caprin-1 P47756 CAPZB F-actin-capping protein subunitbeta Q86X55 CARM1 Histone-arginine methyltransferase CARM1 P49589 CARSCysteine--tRNA ligase, cytoplasmic P20810 CAST Calpastatin P04040 CATCatalase P35520 CBS Cystathionine beta-synthase Q13185 CBX3 Chromoboxprotein homolog 3 P45973 CBX5 Chromobox protein homolog 5 Q96G28 CCDC104Coiled-coil domain-containing protein 104 O60826 CCDC22 Coiled-coildomain-containing protein 22 Q96A33 CCDC47 Coiled-coil domain-containingprotein 47 Q96ER9 CCDC51 Coiled-coil domain-containing protein 51 Q16204CCDC6 Coiled-coil domain-containing protein 6 P78371 CCT2 T-complexprotein 1 subunit beta P49368 CCT3 T-complex protein 1 subunit gammaP50991 CCT4 T-complex protein 1 subunit delta P48643 CCT5 T-complexprotein 1 subunit epsilon P40227 CCT6A T-complex protein 1 subunit zetaQ99832 CCT7 T-complex protein 1 subunit eta P50990 CCT8 T-complexprotein 1 subunit theta O95400 CD2BP2 CD2 antigen cytoplasmic tail-binding protein 2 P60033 CD81 CD81 antigen Q9UJX2 CDC23 Cell divisioncycle protein 23 homolog P30260 CDC27 Cell division cycle protein 27homolog Q16543 CDC37 Hsp90 co-chaperone Cdc37 P60953 CDC42 Cell divisioncontrol protein 42 homolog Q99459 CDC5L Cell division cycle 5-likeprotein P19022 CDH2 Cadherin-2 O14735 CDIPT CDP-diacylglycerol--inositol3- phosphatidyltransfe P06493 CDK1 Cyclin-dependent kinase 1 P24941 CDK2Cyclin-dependent kinase 2 P11802 CDK4 Cyclin-dependent kinase 4 Q96JB5CDK5RAP3 CDK5 regulatory subunit- associated protein 3 Q00534 CDK6Cyclin-dependent kinase 6 P50750 CDK9 Cyclin-dependent kinase 9 Q5VV42CDKAL1 Threonylcarbamoyladenosine tRNA methylthiotransfer O95674 CDS2Phosphatidate cytidylyltransferase 2 Q03701 CEBPZ CCAAT/enhancer-bindingprotein zeta Q9BXW7 CECR5 Cat eye syndrome critical region protein 5Q92879 CELF1 CUGBP Elav-like family member 1 Q5SW79 CEP170 Centrosomalprotein of 170 kDa Q9C0F1 CEP44 Centrosomal protein of 44 kDa Q9Y6K0CEPT1 Choline/ethanolaminephosphotransferase 1 P27544 CERS1 Ceramidesynthase 1 Q96G23 CERS2 Ceramide synthase 2 Q6ZMG9 CERS6 Ceramidesynthase 6 Q9NX63 CHCHD3 Coiled-coil-helix-coiled-coil- helixdomain-contain O14646 CHD1 Chromodomain-helicase-DNA- binding protein 1Q14839 CHD4 Chromodomain-helicase-DNA- binding protein 4 O14757 CHEK1Serine/threonine-protein kinase Chk1 Q8IWX8 CHERP Calcium homeostasisendoplasmic reticulum protein Q9NZZ3 CHMP5 Charged multiyesicular bodyprotein 5 Q14011 CIRBP Cold-inducible RNA-binding protein Q9NZ45 CISD1CDGSH iron-sulfur domain- containing protein 1 Q8N5K1 CISD2 CDGSHiron-sulfur domain- containing protein 2 Q8WWK9 CKAP2Cytoskeleton-associated protein 2 Q07065 CKAP4 Cytoskeleton-associatedprotein 4 P12277 CKB Creatine kinase B-type P12532 CKMT1B Creatinekinase U-type, mitochondrial F5H604 CLASP2 CLIP-associating protein 2Q96S66 CLCC1 Chloride channel CLIC-like protein 1 O14967 CLGN CalmeginO15247 CLIC2 Chloride intracellular channel protein 2 Q9Y696 CLIC4Chloride intracellular channel protein 4 O75503 CLN5Ceroid-lipofuscinosis neuronal protein 5 P54105 CLNS1A Methylosomesubunit pICIn Q9H078 CLPB Caseinolytic peptidase B protein homologQ16740 CLPP Putative ATP-dependent Clp protease proteolytic su O96005CLPTM1 Cleft lip and palate transmembrane protein 1 Q96KA5 CLPTM1L Cleftlip and palate transmembrane protein 1-like P30085 CMPK1 UMP-CMP kinaseQ99439 CNN2 Calponin-2 Q15417 CNN3 Calponin-3 A5YKK6 CNOT1 CCR4-NOTtranscription complex subunit 1 Q9NZN8 CNOT2 CCR4-NOT transcriptioncomplex subunit 2 P09543 CNP 2,3-cyclic-nucleotide 3- phosphodiesteraseQ9BT09 CNPY3 Protein canopy homolog 3 Q9Y2R0 COA3 Cytochrome C oxidaseassembly factor 3 homolog, mi Q13057 COASY Bifunctional coenzyme Asynthase P21964 COMT Catechol O-methyltransferase P53618 COPB1 Coatomersubunit beta P35606 COPB2 Coatomer subunit beta 014579 COPE Coatomersubunit epsilon Q9Y678 COPG1 Coatomer subunit gamma-1 Q9UBF2 COPG2Coatomer subunit gamma-2 P61201 COPS2 COP9 signalosome complex subunit 2Q9UNS2 COPS3 COP9 signalosome complex subunit 3 Q9BT78 COPS4 COP9signalosome complex subunit 4 Q92905 COPS5 COP9 signalosome complexsubunit 5 Q7L5N1 COPS6 COP9 signalosome complex subunit 6 Q5HYK3 COQ52-methoxy-6-polyprenyl-1,4- benzoquinol methylase, Q9ULV4 CORO1CCoronin-1C I3L416 CORO7 Coronin Q9Y6N1 COX11 Cytochrome c oxidaseassembly protein COX11, mitoc Q7KZN9 COX15 Cytochrome c oxidase assemblyprotein COX15 homolo P13073 COX4I1 Cytochrome c oxidase subunit 4isoform 1, mitochon P20674 COX5A Cytochrome c oxidase subunit 5A,mitochondrial O75976 CPD Carboxypeptidase D Q99829 CPNE1 Copine-1 O75131CPNE3 Copine-3 P36551 CPOX Coproporphyrinogen-III oxidase, mitochondrialQ9BRF8 CPPED1 Calcineurin-like phosphoesterase domain-containing Q9UKF6CPSF3 Cleavage and polyadenylation specificity factor su Q16630 CPSF6Cleavage and polyadenylation specificity factor su Q8N684 CPSF7 Cleavageand polyadenylation specificity factor su P50416 CPT1A CarnitineO-palmitoyltransferase 1, liver isoform P23786 CPT2 CarnitineO-palmitoyltransferase 2, mitochondrial Q9H3G5 CPVL Probable serinecarboxypeptidase CPVL P46108 CRK Adapter molecule crk P46109 CRKLCrk-like protein O75390 CS Citrate synthase, mitochondrial P16989 CSDADNA-binding protein A O75534 CSDE1 Cold shock domain-containing proteinE1 P55060 CSE1L Exportin-2 P41240 CSK Tyrosine-protein kinase CSK P48729CSNK1A1 Casein kinase I isoform alpha P49674 CSNK1E Casein kinase Iisoform epsilon P68400 CSNK2A1 Casein kinase II subunit alpha P19784CSNK2A2 Casein kinase II subunit alpha P67870 CSNK2B Casein kinase IIsubunit beta P04080 CSTB Cystatin-B Q05048 CSTF1 Cleavage stimulationfactor subunit 1 P33240 CSTF2 Cleavage stimulation factor subunit 2Q12996 CSTF3 Cleavage stimulation factor subunit 3 O15320 CTAGE5Cutaneous T-cell lymphoma- associated antigen 5 Q13363 CTBP1C-terminal-binding protein 1 P32929 CTH Cystathionine gamma-lyase P35221CTNNA1 Catenin alpha-1 P35222 CTNNB1 Catenin beta-1 O60716 CTNND1Catenin delta-1 P17812 CTPS1 CTP synthase 1 P10619 CTSA Lysosomalprotective protein P07858 CTSB Cathepsin B P53634 CTSC Dipeptidylpeptidase 1 P07339 CTSD Cathepsin D Q14247 CTTN Src substrate cortactinQ13620 CUL4B Cullin-4B O60888 CUTA Protein CutA Q69YN2 CWF19L1CWF19-like protein 1 Q9BVG4 CXorf26 UPF0368 protein Cxorf26 P00167 CYB5ACytochrome b5 O43169 CYB5B Cytochrome b5 type B Q8WUJ1 CYB5D2Neuferricin Q9UHQ9 CYB5R1 NADH-cytochrome b5 reductase 1 P00387 CYB5R3NADH-cytochrome b5 reductase 3 P08574 CYC1 Cytochrome c1, heme protein,mitochondrial Q7L576 CYFIP1 Cytoplasmic FMR1-interacting protein 1Q6UW02 CYP20A1 Cytochrome P450 20A1 Q16850 CYP51A1 Lanosterol 14-alphademethylase P51398 DAP3 28S ribosomal protein S29, mitochondrial P14868DARS Aspartate--tRNA ligase, cytoplasmic Q6PI48 DARS2 Aspartate--tRNAligase, mitochondrial Q96EP5 DAZAP1 DAZ-associated protein 1 Q16643 DBN1Drebrin Q9UJU6 DBNL Drebrin-like protein P61962 DCAF7 DDB1- andCUL4-associated factor 7 Q8WVC6 DCAKD Dephospho-CoA kinase domain-containing protein P81605 DCD Dermcidin Q14203 DCTN1 Dynactin subunit 1Q13561 DCTN2 Dynactin subunit 2 Q9UJW0 DCTN4 Dynactin subunit 4 Q9H773DCTPP1 dCTP pyrophosphatase 1 Q92564 DCUN1D4 DCN1-like protein 4 Q7Z4W1DCXR L-xylulose reductase Q16531 DDB1 DNA damage-binding protein 1P39656 DDOST Dolichyl- diphosphooligosaccharide--protein glycosy Q96HY6DDRGK1 DDRGK domain-containing protein 1 Q13206 DDX10 ProbableATP-dependent RNA helicase DDX10 Q92841 DDX17 Probable ATP-dependent RNAhelicase DDX17 Q9NVP1 DDX18 ATP-dependent RNA helicase DDX18 Q9UHI6DDX20 Probable ATP-dependent RNA helicase DDX20 Q9NR30 DDX21 NucleolarRNA helicase 2 Q9BUQ8 DDX23 Probable ATP-dependent RNA helicase DDX23Q9GZR7 DDX24 ATP-dependent RNA helicase DDX24 O00148 DDX39AATP-dependent RNA helicase DDX39A Q13838 DDX39B Spliceosome RNA helicaseDDX39B O00571 DDX3X ATP-dependent RNA helicase DDX3X Q86XP3 DDX42ATP-dependent RNA helicase DDX42 Q7L014 DDX46 Probable ATP-dependent RNAhelicase DDX46 P17844 DDX5 Probable ATP-dependent RNA helicase DDX5Q9BQ39 DDX50 ATP-dependent RNA helicase DDX50 Q8TDD1 DDX54 ATP-dependentRNA helicase DDX54 P26196 DDX6 Probable ATP-dependent RNA helicase DDX6Q16698 DECR1 2,4-dienoyl-CoA reductase, mitochondrial O15121 DEGS1Sphingolipid delta(4)-desaturase DES1 Q9BUN8 DERL1 Derlin-1 Q9BSY9 DESI2Desumoylating isopeptidase 2 O00273 DFFA DNA fragmentation factorsubunit alpha Q96DF8 DGCR14 Protein DGCR14 Q15392 DHCR24Delta(24)-sterol reductase P00374 DHFR Dihydrofolate reductase P49366DHPS Deoxyhypusine synthase Q9Y394 DHRS7 Dehydrogenase/reductase SDRfamily member 7 Q6IAN0 DHRS7B Dehydrogenase/reductase SDR family member7B O43143 DHX15 Putative pre-mRNA-splicing factor ATP-dependent RNQ7Z478 DHX29 ATP-dependent RNA helicase DHX29 Q7L2E3 DHX30 PutativeATP-dependent RNA helicase DHX30 Q9H2U1 DHX36 Probable ATP-dependent RNAhelicase DHX36 Q14562 DHX8 ATP-dependent RNA helicase DHX8 Q08211 DHX9ATP-dependent RNA helicase A Q9NR28 DIABLO Diablo homolog, mitochondrialO60610 DIAPH1 Protein diaphanous homolog 1 Q9Y2L1 DIS3 Exosome complexexonuclease RRP44 P10515 DLAT Dihydrolipoyllysine-residueacetyltransferase comp P09622 DLD Dihydrolipoyl dehydrogenase,mitochondrial Q15398 DLGAP5 Disks large-associated protein 5 P31689DNAJA1 DnaJ homolog subfamily A member 1 O60884 DNAJA2 DnaJ homologsubfamily A member 2 Q96EY1 DNAJA3 DnaJ homolog subfamily A member 3,mitochondrial P25685 DNAJB1 DnaJ homolog subfamily B member 1 Q9NXW2DNAJB12 DnaJ homolog subfamily B member 12 Q96KC8 DNAJC1 DnaJ homologsubfamily C member 1 Q8IXB1 DNAJC10 DnaJ homolog subfamily C member 10Q9NVH1 DNAJC11 DnaJ homolog subfamily C member 11 Q99543 DNAJC2 DnaJhomolog subfamily C member 2 Q9H3Z4 DNAJC5 DnaJ homolog subfamily Cmember 5 Q99615 DNAJC7 DnaJ homolog subfamily C member 7 O75937 DNAJC8DnaJ homolog subfamily C member 8 Q8WXX5 DNAJC9 DnaJ homolog subfamily Cmember 9 O00115 DNASE2 Deoxyribonuclease-2-alpha Q05193 DNM1 Dynamin-1O00429 DNM1L Dynamin-1-like protein P50570 DNM2 Dynamin-2 Q9UQ16 DNM3Dynamin-3 Q9BU89 DOHH Deoxyhypusine hydroxylase Q9UPQ8 DOLK Dolicholkinase Q86YN1 DOLPP1 Dolichyldiphosphatase 1 O60762 DPM1Dolichol-phosphate mannosyltransferase Q9NY33 DPP3 Dipeptidyl peptidase3 Q9UHL4 DPP7 Dipeptidyl peptidase 2 Q9Y295 DRG1Developmentally-regulated GTP- binding protein 1 Q08554 DSC1Desmocollin-1 Q02413 DSG1 Desmoglein-1 P15924 DSP Desmoplakin P60981DSTN Destrin Q14204 DYNC1H1 Cytoplasmic dynein 1 heavy chain 1 Q13409DYNC1I2 Cytoplasmic dynein 1 intermediate chain 2 Q9Y6G9 DYNC1LI1Cytoplasmic dynein 1 light intermediate chain 1 P63167 DYNLL1 Dyneinlight chain 1, cytoplasmic Q96FJ2 DYNLL2 Dynein light chain 2,cytoplasmic Q99848 EBNA1BP2 Probable rRNA-processing protein EBP2 O95905ECD Protein SGT1 P42892 ECE1 Endothelin-converting enzyme 1 Q13011 ECH1Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitoc Q9NTX5 ECHDC1Ethylmalonyl-CoA decarboxylase P30084 ECHS1 Enoyl-CoA hydratase,mitochondrial P42126 ECI1 Enoyl-CoA delta isomerase 1, mitochondrialO75521 ECI2 Enoyl-CoA delta isomerase 2, mitochondrial Q5VYK3 ECM29Proteasome-associated protein ECM29 homolog Q6P2E9 EDC4 Enhancer ofmRNA-decapping protein 4 P68104 EEF1A1 Elongation factor 1-alpha 1Q5VTE0 EEF1A1P5 Putative elongation factor 1- alpha-like 3 P24534 EEF1B2Elongation factor 1-beta E9PRY8 EEF1D Elongation factor 1-delta P26641EEF1G Elongation factor 1-gamma P13639 EEF2 Elongation factor 2 Q8IYU8EFHA1 EF-hand domain-containing family member A1 Q15029 EFTUD2 116 kDaU5 small nuclear ribonucleoprotein compone Q9H4M9 EHD1 EHdomain-containing protein 1 Q9H223 EHD4 EH domain-containing protein 4O14681 EI24 Etoposide-induced protein 2.4 homolog Q9BY44 EIF2AEukaryotic translation initiation factor 2A P19525 EIF2AK2Interferon-induced, double- stranded RNA-activated Q9NR50 EIF2B3Translation initiation factor eIF- 2B subunit gamma P05198 EIF2S1Eukaryotic translation initiation factor 2 subunit P20042 EIF2S2Eukaryotic translation initiation factor 2 subunit P41091 EIF2S3Eukaryotic translation initiation factor 2 subunit Q14152 EIF3AEukaryotic translation initiation factor 3 subunit P55884 EIF3BEukaryotic translation initiation factor 3 subunit B5ME19 EIF3CLEukaryotic translation initiation factor 3 subunit O15371 EIF3DEukaryotic translation initiation factor 3 subunit P60228 EIF3EEukaryotic translation initiation factor 3 subunit B0QY89 EIF3EIPEukaryotic translation initiation factor 3 subunit O00303 EIF3FEukaryotic translation initiation factor 3 subunit O75821 EIF3GEukaryotic translation initiation factor 3 subunit O15372 EIF3HEukaryotic translation initiation factor 3 subunit Q13347 EIF3IEukaryotic translation initiation factor 3 subunit O75822 EIF3JEukaryotic translation initiation factor 3 subunit Q9Y262 EIF3LEukaryotic translation initiation factor 3 subunit Q7L2H7 EIF3MEukaryotic translation initiation factor 3 subunit P60842 EIF4A1Eukaryotic initiation factor 4A-I Q14240 EIF4A2 Eukaryotic initiationfactor 4A-II P38919 EIF4A3 Eukaryotic initiation factor 4A-III P23588EIF4B Eukaryotic translation initiation factor 4B P06730 EIF4EEukaryotic translation initiation factor 4E Q04637 EIF4G1 Eukaryotictranslation initiation factor 4 gamma 1 P78344 EIF4G2 Eukaryotictranslation initiation factor 4 gamma 2 Q15056 EIF4H Eukaryotictranslation initiation factor 4H P55010 EIF5 Eukaryotic translationinitiation factor 5 P63241 EIF5A Eukaryotic translation initiationfactor 5A-1 Q9GZV4 EIF5A2 Eukaryotic translation initiation factor 5A-2O60841 EIF5B Eukaryotic translation initiation factor 5B P56537 EIF6Eukaryotic translation initiation factor 6 Q9BQ52 ELAC2 Zincphosphodiesterase ELAC protein 2 Q15717 ELAVL1 ELAV-like protein 1Q8IZ81 ELMOD2 ELMO domain-containing protein 2 Q9NXB9 ELOVL2 Elongationof very long chain fatty acids protein Q8N766 EMC1 ER membrane proteincomplex subunit 1 Q9NPA0 EMC7 ER membrane protein complex subunit 7P50402 EMD Emerin O94919 ENDOD1 Endonuclease domain- containing 1protein Q9UHY7 ENOPH1 Enolase-phosphatase E1 P11171 EPB41 Protein 4.1O43491 EPB41L2 Band 4.1-like protein 2 Q9UM22 EPDR1 Mammalianependymin-related protein 1 P07099 EPHX1 Epoxide hydrolase 1 P34913EPHX2 Bifunctional epoxide hydrolase 2 P07814 EPRS Bifunctionalglutamate/proline-- tRNA ligase P42566 EPS15 Epidermal growth factorreceptor substrate 15 Q9UBC2 EPS15L1 Epidermal growth factor receptorsubstrate 15-like Q9NZ08 ERAP1 Endoplasmic reticulum aminopeptidase 1Q9Y282 ERGIC3 Endoplasmic reticulum-Golgi intermediate compartme P84090ERH Enhancer of rudimentary homolog O75477 ERLIN1 Erlin-1 O94905 ERLIN2Erlin-2 Q96HE7 ERO1L ERO1-like protein alpha P30040 ERP29 Endoplasmicreticulum resident protein 29 Q9B526 ERP44 Endoplasmic reticulumresident protein 44 Q9BSJ8 ESYT1 Extended synaptotagmin-1 A0FGR8 ESYT2Extended synaptotagmin-2 P62495 ETF1 Eukaryotic peptide chain releasefactor subunit 1 P13804 ETFA Electron transfer flavoprotein subunitalpha, mito P38117 ETFB Electron transfer flavoprotein subunit betaQ16134 ETFDH Electron transfer flavoprotein- ubiquinone oxidored Q01844EWSR1 RNA-binding protein EWS Q9UQ84 EXO1 Exonuclease 1 Q96KP1 EXOC2Exocyst complex component 2 Q96A65 EXOC4 Exocyst complex component 4O00471 EXOC5 Exocyst complex component 5 Q01780 EXOSC10 Exosomecomponent 10 Q9NQT5 EXOSC3 Exosome complex component RRP40 P15311 EZREzrin Q9Y624 F11R Junctional adhesion molecule A O60427 FADS1 Fatty aciddesaturase 1 O95864 FADS2 Fatty acid desaturase 2 Q9UNN5 FAF1FAS-associated factor 1 Q96CS3 FAF2 FAS-associated factor 2 P16930 FAHFumarylacetoacetase Q9NRY5 FAM114A2 Protein FAM114A2 Q96TA1 FAM129BNiban-like protein 1 Q96A26 FAM162A Protein FAM162A Q9BTY7 FAM203AProtein FAM203A P0CB43 FAM203B Protein FAM203B Q9UK61 FAM208A ProteinFAM208A Q9BRX8 FAM213A Redox-regulatory protein FAM213A Q92520 FAM3CProtein FAM3C Q9NUQ9 FAM49B Protein FAM49B Q9H019 FAM54B Protein FAM54BQ96TC7 FAM82A2 Regulator of microtubule dynamics protein 3 Q96DB5 FAM82BRegulator of microtubule dynamics protein 1 Q9UBU6 FAM8A1 Protein FAM8A1Q8NCA5 FAM98A Protein FAM98A Q52LJ0 FAM98B Protein FAM98B Q9NVI1 FANCIFanconi anemia group I protein Q8WVX9 FAR1 Fatty acyl-CoA reductase 1Q9Y285 FARSA Phenylalanine--tRNA ligase alpha subunit Q9NSD9 FARSBPhenylalanine--tRNA ligase beta subunit P49327 FASN Fatty acid synthaseP22087 FBL rRNA 2-O-methyltransferase fibrillarin P37268 FDFT1 Squalenesynthase P22830 FECH Ferrochelatase, mitochondrial P39748 FEN1 Flapendonuclease 1 Q86UX7 FERMT3 Fermitin family homolog 3 O95684 FGFR1OPFGFR1 oncogene partner P07954 FH Fumarate hydratase, mitochondrialQ9Y613 FHOD1 FH1/FH2 domain-containing protein 1 Q6UN15 FIP1L1 Pre-mRNA3-end-processing factor FIP1 Q96AY3 FKBP10 Peptidyl-prolyl cis-transisomerase FKBP10 Q9NWM8 FKBP14 Peptidyl-prolyl cis-trans isomeraseFKBP14 P62942 FKBP1A Peptidyl-prolyl cis-trans isomerase FKBP1A Q00688FKBP3 Peptidyl-prolyl cis-trans isomerase FKBP3 Q02790 FKBP4Peptidyl-prolyl cis-trans isomerase FKBP4 Q13451 FKBP5 Peptidyl-prolylcis-trans isomerase FKBP5 Q9Y680 FKBP7 Peptidyl-prolyl cis-transisomerase FKBP7 Q14318 FKBP8 Peptidyl-prolyl cis-trans isomerase FKBP8Q8NFF5 FLAD1 FAD synthase Q13045 FLII Protein flightless-1 homologQ14315 FLNC Filamin-C O75955 FLOT1 Flotillin-1 Q14254 FLOT2 Flotillin-2Q06787 FMR1 Fragile X mental retardation protein 1 Q9H479 FN3KFructosamine-3-kinase P49354 FNTA Proteinfarnesyltransferase/geranylgeranyltransfer Q96CU9 FOXRED1 FAD-dependentoxidoreductase domain-containing pro Q16658 FSCN1 Fascin Q8IY81 FTSJ3pre-rRNA processing protein FTSJ3 Q96AE4 FUBP1 Far upstreamelement-binding protein 1 Q96I24 FUBP3 Far upstream element-bindingprotein 3 P04066 FUCA1 Tissue alpha-L-fucosidase Q9BTY2 FUCA2 Plasmaalpha-L-fucosidase P35637 FUS RNA-binding protein FUS P51114 FXR1Fragile X mental retardation syndrome-related prot P51116 FXR2 Fragile Xmental retardation syndrome-related prot Q13283 G3BP1 RasGTPase-activating protein- binding protein 1 Q9UN86 G3BP2 RasGTPase-activating protein- binding protein 2 P11413 G6PDGlucose-6-phosphate 1- dehydrogenase P10253 GAA Lysosomalalpha-glucosidase O14976 GAK Cyclin-G-associated kinase Q10472 GALNT1Polypeptide N- acetylgalactosaminyltransferase 1 Q10471 GALNT2Polypeptide N- acetylgalactosaminyltransferase 2 Q8N4A0 GALNT4Polypeptide N- acetylgalactosaminyltransferase 4 Q14697 GANAB Neutralalpha-glucosidase AB Q14C86 GAPVD1 GTPase-activating protein and VPS9domain-containi P41250 GARS Glycine--tRNA ligase P22102 GARTTrifunctional purine biosynthetic protein adenosin P04062 GBAGlucosylceramidase O75323 GBAS Protein NipSnap homolog 2 Q92538 GBF1Golgi-specific brefeldin A- resistance guanine nucl O75600 GCAT2-amino-3-ketobutyrate coenzyme A ligase, mitochon Q92616 GCN1L1Translational activator GCN1 P31150 GDI1 Rab GDP dissociation inhibitoralpha P50395 GDI2 Rab GDP dissociation inhibitor beta Q8N9F7 GDPD1Glycerophosphodiester phosphodiesterase domain-con Q7L5D6 GET4 Golgi toER traffic protein 4 homolog Q96RP9 GFM1 Elongation factor G,mitochondrial Q06210 GFPT1 Glucosamine--fructose-6- phosphateaminotransferase P38435 GGCX Vitamin K-dependent gamma- carboxylaseQ92820 GGH Gamma-glutamyl hydrolase Q9UJ14 GGT7Gamma-glutamyltransferase 7 Q9H3K2 GHITM Growth hormone-inducibletransmembrane protein Q6Y7W6 GIGYF2 PERQ amino acid-rich with GYFdomain-containing pr P32189 GK Glycerol kinase P06280 GLAAlpha-galactosidase A P16278 GLB1 Beta-galactosidase Q92896 GLG1 Golgiapparatus protein 1 Q04760 GLO1 Lactoylglutathione lyase Q9HC38 GLOD4Glyoxalase domain-containing protein 4 O76003 GLRX3 Glutaredoxin-3O94925 GLS Glutaminase kidney isoform, mitochondrial Q68CQ7 GLT8D1Glycosyltransferase 8 domain- containing protein 1 P00367 GLUD1Glutamate dehydrogenase 1, mitochondrial P49448 GLUD2 Glutamatedehydrogenase 2, mitochondrial P17900 GM2A Ganglioside GM2 activatorP49915 GMPS GMP synthase [glutamine- hydrolyzing] P04899 GNAI2 Guaninenucleotide-binding protein G(i) subunit al P08754 GNAI3 Guaninenucleotide-binding protein G(k) subunit al P62873 GNB1 Guaninenucleotide-binding protein G(I)/G(S)/G(T) P62879 GNB2 Guaninenucleotide-binding protein G(I)/G(S)/G(T) P63244 GNB2L1 Guaninenucleotide-binding protein subunit beta-2- Q13823 GNL2 NucleolarGTP-binding protein 2 Q9BVP2 GNL3 Guanine nucleotide-binding protein-like 3 O15228 GNPAT Dihydroxyacetone phosphate acyltransferase P15586GNS N-acetylglucosamine-6-sulfatase Q08378 GOLGA3 Golgin subfamily Amember 3 Q8TBA6 GOLGA5 Golgin subfamily A member 5 O00461 GOLIM4 Golgiintegral membrane protein 4 Q8NBJ4 GOLM1 Golgi membrane protein 1 Q9H4A6GOLPH3 Golgi phosphoprotein 3 Q9H4A5 GOLPH3L Golgi phosphoprotein 3-likeQ9HD26 GOPC Golgi-associated PDZ and coiled- coil motif-contain O95249GOSR1 Golgi SNAP receptor complex member 1 P00505 GOT2 Aspartateaminotransferase, mitochondrial O43292 GPAA1Glycosylphosphatidylinositol anchor attachment 1 p Q9HCL2 GPAMGlycerol-3-phosphate acyltransferase 1, mitochondr P43304 GPD2Glycerol-3-phosphate dehydrogenase, mitochondrial Q5VW38 GPR107 ProteinGPR107 P0CG08 GPR89B Golgi pH regulator B P36969 GPX4 Phospholipidhydroperoxide glutathione peroxidase, Q8TED1 GPX8 Probable glutathioneperoxidase 8 P62993 GRB2 Growth factor receptor-bound protein 2 Q9UBQ7GRHPR Glyoxylate reductase/hydroxypyruvate reductase Q9HAV7 GRPEL1 GrpEprotein homolog 1, mitochondrial Q12849 GRSF1 G-rich sequence factor 1Q9BQ67 GRWD1 Glutamate-rich WD repeat- containing protein 1 P15170 GSPT1Eukaryotic peptide chain release factor GTP-bindin Q8IYD1 GSPT2Eukaryotic peptide chain release factor GTP-bindin P00390 GSRGlutathione reductase, mitochondrial P48637 GSS Glutathione synthetaseQ9Y2Q3 GSTK1 Glutathione S-transferase kappa 1 P21266 GSTM3 GlutathioneS-transferase Mu 3 P78417 GSTO1 Glutathione S-transferase omega-1 P09211GSTP1 Glutathione S-transferase P P78347 GTF21 General transcriptionfactor II-I Q9Y5Q9 GTF3C3 General transcription factor 3C polypeptide 3O00178 GTPBP1 GTP-binding protein 1 Q9BZE4 GTPBP4 Nucleolar GTP-bindingprotein 1 P08236 GUSB Beta-glucuronidase P13807 GYS1 Glycogen P16104H2AFX Histone H2A.x O75367 H2AFY Core histone macro-H2A.1 P0C0S5 H2AFZHistone H2A.Z Q16836 HADH Hydroxyacyl-coenzyme A dehydrogenase,mitochondria P40939 HADHA Trifunctional enzyme subunit alpha,mitochondrial P55084 HADHB Trifunctional enzyme subunit beta,mitochondrial P12081 HARS Histidine--tRNA ligase, cytoplasmic O14929HAT1 Histone acetyltransferase type B catalytic subunit Q96CS2 HAUS1HAUS augmin-like complex subunit 1 Q9NVX0 HAUS2 HAUS augmin-like complexsubunit 2 Q68CZ6 HAUS3 HAUS augmin-like complex subunit 3 Q9H6D7 HAUS4HAUS augmin-like complex subunit 4 O94927 HAUS5 HAUS augmin-like complexsubunit 5 O00165 HAX1 HCLS1-associated protein X-1 P69905 HBA2Hemoglobin subunit alpha P68871 HBB Hemoglobin subunit beta P02100 HBE1Hemoglobin subunit epsilon P69891 HBG1 Hemoglobin subunit gamma-1 P69892HBG2 Hemoglobin subunit gamma-2 Q9Y450 HBS1L HBS1-like protein P02008HBZ Hemoglobin subunit zeta P53701 HCCS Cytochrome c-type heme lyaseQ13547 HDAC1 Histone deacetylase 1 Q92769 HDAC2 Histone deacetylase 2P51858 HDGF Hepatoma-derived growth factor Q9BSH5 HDHD3 Haloaciddehalogenase-like hydrolase domain-contai Q00341 HDLBP Vigilin Q9H583HEATR1 HEAT repeat-containing protein 1 Q86Y56 HEATR2 HEATrepeat-containing protein 2 Q7Z4Q2 HEATR3 HEAT repeat-containing protein3 Q9NRZ9 HELLS Lymphoid-specific helicase Q9BXL5 HEMGN Hemogen P06865HEXA Beta-hexosaminidase subunit alpha P07686 HEXB Beta-hexosaminidasesubunit beta P31937 HIBADH 3-hydroxyisobutyrate dehydrogenase,mitochondrial Q6NVY1 HIBCH 3-hydroxyisobutyryl-CoA hydrolase,mitochondrial Q9Y241 HIGD1A HIG1 domain family member 1A P49773 HINT1Histidine triad nucleotide-binding protein 1 Q9NQE9 HINT3 Histidinetriad nucleotide-binding protein 3 P16403 HIST1H1C Histone H1.2 P16402HIST1H1D Histone H1.3 Q16777 HIST2H2AC Histone H2A type 2-C P19367 HK1Hexokinase-1 P52789 HK2 Hexokinase-2 P30443 HLA-A HLA class Ihistocompatibility antigen, A-1 alpha P01892 HLA-A HLA class Ihistocompatibility antigen, A-2 alpha P04439 HLA-A HLA class Ihistocompatibility antigen, A-3 alpha P01891 HLA-A HLA class Ihistocompatibility antigen, A-68 alpha P30462 HLA-B HLA class Ihistocompatibility antigen, B-14 alpha P18463 HLA-B HLA class Ihistocompatibility antigen, B-37 alpha Q29940 HLA-B HLA class Ihistocompatibility antigen, B-59 alpha Q31612 HLA-B HLA class Ihistocompatibility antigen, B-73 alpha P30460 HLA-B HLA class Ihistocompatibility antigen, B-8 alpha P30499 HLA-C HLA class Ihistocompatibility antigen, Cw-1 alpha F8VZB9 HLA-C HLA class Ihistocompatibility antigen, Cw-14 alph Q07000 HLA-C HLA class Ihistocompatibility antigen, Cw-15 alph Q29963 HLA-C HLA class Ihistocompatibility antigen, Cw-6 alpha P10321 HLA-C HLA class Ihistocompatibility antigen, Cw-7 alpha Q8TCT9 HM13 Minorhistocompatibility antigen H13 P09429 HMGB1 High mobility group proteinB1 P26583 HMGB2 High mobility group protein B2 O15347 HMGB3 Highmobility group protein B3 Q01581 HMGCS1 Hydroxymethylglutaryl-CoAsynthase, cytoplasmic P09601 HMOX1 Heme oxygenase 1 P30519 HMOX2 Hemeoxygenase 2 Q13151 HNRNPA0 Heterogeneous nuclear ribonucleoprotein A0P09651 HNRNPA1 Heterogeneous nuclear ribonucleoprotein A1 Q32P51HNRNPA1L2 Heterogeneous nuclear ribonucleoprotein A1-like 2 P22626HNRNPA2B1 Heterogeneous nuclear ribonucleoproteins A2/B1 P51991 HNRNPA3Heterogeneous nuclear ribonucleoprotein A3 Q99729 HNRNPAB Heterogeneousnuclear ribonucleoprotein A/B P07910 HNRNPC Heterogeneous nuclearribonucleoproteins C1/C2 O60812 HNRNPCL1 Heterogeneous nuclearribonucleoprotein C-like 1 Q14103 HNRNPD Heterogeneous nuclearribonucleoprotein D0 P52597 HNRNPF Heterogeneous nuclearribonucleoprotein F P31943 HNRNPH1 Heterogeneous nuclearribonucleoprotein H P55795 HNRNPH2 Heterogeneous nuclearribonucleoprotein H2 P31942 HNRNPH3 Heterogeneous nuclearribonucleoprotein H3 P61978 HNRNPK Heterogeneous nuclearribonucleoprotein K P14866 HNRNPL Heterogeneous nuclearribonucleoprotein L P52272 HNRNPM Heterogeneous nuclearribonucleoprotein M O43390 HNRNPR Heterogeneous nuclearribonucleoprotein R Q00839 HNRNPU Heterogeneous nuclearribonucleoprotein U Q9BUJ2 HNRNPUL1 Heterogeneous nuclearribonucleoprotein U-like pro Q1KMD3 HNRNPUL2 Heterogeneous nuclearribonucleoprotein U-like pro O14979 HNRPDL Heterogeneous nuclearribonucleoprotein D-like Q8WVV9 HNRPLL Heterogeneous nuclearribonucleoprotein L-like Q5SSJ5 HP1BP3 Heterochromatin protein 1-binding protein 3 P37235 HPCAL1 Hippocalcin-like protein 1 P00492 HPRT1Hypoxanthine-guanine phosphoribosyltransferase Q86YZ3 HRNR HornerinQ7LGA3 HS2ST1 Heparan sulfate 2-O- sulfotransferase 1 Q99714 HSD17B103-hydroxyacyl-CoA dehydrogenase type-2 Q8NBQ5 HSD17B11 Estradiol17-beta- dehydrogenase 11 Q53GQ0 HSD17B12 Estradiol 17-beta-dehydrogenase 12 P51659 HSD17B4 Peroxisomal multifunctional enzyme type2 Q3SXM5 HSDL1 Inactive hydroxysteroid dehydrogenase-like protein Q6YN16HSDL2 Hydroxysteroid dehydrogenase- like protein 2 P07900 HSP90AA1 Heatshock protein HSP 90- alpha P08238 HSP90AB1 Heat shock protein HSP 90-beta P14625 HSP90B1 Endoplasmin Q0VDF9 HSPA14 Heat shock 70 kDa protein14 P08107 HSPA1A Heat shock 70 kDa protein 1A/1B P34931 HSPA1L Heatshock 70 kDa protein 1-like P11021 HSPA5 78 kDa glucose-regulatedprotein P17066 HSPA6 Heat shock 70 kDa protein 6 P11142 HSPA8 Heat shockcognate 71 kDa protein P38646 HSPA9 Stress-70 protein, mitochondrialP04792 HSPB1 Heat shock protein beta-1 Q9NZL4 HSPBP1 Hsp70-bindingprotein 1 P10809 HSPD1 60 kDa heat shock protein, mitochondrial P61604HSPE1 10 kDa heat shock protein, mitochondrial Q92598 HSPH1 Heat shockprotein 105 kDa O43719 HTATSF1 HIV Tat-specific factor 1 Q7Z6Z7 HUWE1 E3ubiquitin-protein ligase HUWE1 Q9Y4L1 HYOU1 Hypoxia up-regulated protein1 P41252 IARS Isoleucine--tRNA ligase, cytoplasmic Q9NSE4 IARS2Isoleucine--tRNA ligase, mitochondrial O60725 ICMTProtein-S-isoprenylcysteine O- methyltransferase P14735 IDEInsulin-degrading enzyme O75874 IDH1 Isocitrate dehydrogenase [NADP]cytoplasmic P48735 IDH2 Isocitrate dehydrogenase P50213 IDH3A Isocitratedehydrogenase O43837 IDH3B Isocitrate dehydrogenase [NAD] subunit beta,mitoc P13284 IF130 Gamma-interferon-inducible lysosomal thiol reductaQ9NZI8 IGF2BP1 Insulin-like growth factor 2 mRNA-binding protein Q9Y6M1IGF2BP2 Insulin-like growth factor 2 mRNA-binding protein O00425 IGF2BP3Insulin-like growth factor 2 mRNA-binding protein Q13123 IK Protein RedQ12905 ILF2 Interleukin enhancer-binding factor 2 Q12906 ILF3Interleukin enhancer-binding factor 3 A1L0T0 ILVBL Acetolactatesynthase-like protein Q16891 IMMT Mitochondrial inner membrane proteinQ9NX62 IMPAD1 Inositol monophosphatase 3 P12268 IMPDH2Inosine-5-monophosphate dehydrogenase 2 Q16352 INA Alpha-internexinQ9UI26 IPO11 Importin-11 Q8IEX9 IPO4 Importin-4 O00410 IPO5 Importin-5O95373 IPO7 Importin-7 O15397 IPO8 Importin-8 Q96P70 IPO9 Importin-9P46940 IQGAP1 Ras GTPase-activating-like protein IQGAP1 O14654 IRS4Insulin receptor substrate 4 Q96CN7 ISOC1 Isochorismatasedomain-containing protein 1 Q96J02 ITCH E3 ubiquitin-protein ligaseItchy homolog Q9Y287 ITM2B Integral membrane protein 2B Q8N5M9 JAGN1Protein jagunal homolog 1 P14923 JUP Junction plakoglobin Q15046 KARSLysine-tRNA ligase Q96CX2 KCTD12 BTB/POZ domain-containing proteinKCTD12 P24390 KDELR1 ER lumen protein retaining receptor 1 P33947 KDELR2ER lumen protein retaining receptor 2 O43731 KDELR3 ER lumen proteinretaining receptor 3 Q8NB78 KDM1B Lysine-specific histone demethylase 1BQ06136 KDSR 3-ketodihydrosphingosine reductase Q07666 KHDRBS1 KHdomain-containing, RNA- binding, signal transduc Q92945 KHSRP Farupstream element-binding protein 2 Q15397 KIAA0020 Pumiliodomain-containing protein KIAA0020 O75153 KIAA0664 Clusteredmitochondria protein homolog Q2M389 KIAA1033 WASH complex subunit 7Q96EK5 KIAA1279 KIF1-binding protein Q8N163 KIAA1967 DBIRD complexsubunit KIAA1967 Q8IYS2 KIAA2013 Uncharacterized protein KIAA2013 P52732KIF11 Kinesin-like protein KIF11 Q14807 KIF22 Kinesin-like protein KIF22Q99661 KIF2C Kinesin-like protein KIF2C P33176 KIF5B Kinesin-1 heavychain Q07866 KLC1 Kinesin light chain 1 Q9H0B6 KLC2 Kinesin light chain2 P50748 KNTC1 Kinetochore-associated protein 1 P52294 KPNA1 Importinsubunit alpha-1 P52292 KPNA2 Importin subunit alpha-2 O00505 KPNA3Importin subunit alpha-3 O00629 KPNA4 Importin subunit alpha-4 O60684KPNA6 Importin subunit alpha-7 Q14974 KPNB1 Importin subunit beta-1Q5T749 KPRP Keratinocyte proline-rich protein Q86UP2 KTN1 KinectinQ9H9P8 L2HGDH L-2-hydroxyglutarate dehydrogenase, mitochondrial P11279LAMP1 Lysosome-associated membrane glycoprotein 1 P13473 LAMP2Lysosome-associated membrane glycoprotein 2 Q6IAA8 LAMTOR1 Ragulatorcomplex protein LAMTOR1 P28838 LAP3 Cytosol aminopeptidase Q6PKG0 LARP1La-related protein 1 Q71RC2 LARP4 La-related protein 4 Q92615 LARP4BLa-related protein 4B Q9P2J5 LARS Leucine--tRNA ligase, cytoplasmicQ15031 LARS2 Probable leucine--tRNA ligase, mitochondrial Q9Y4W2 LAS1LRibosomal biogenesis protein LAS1L Q14739 LBR Lamin-B receptor P00338LDHA L-lactate dehydrogenase A chain P07195 LDHB L-lactate dehydrogenaseB chain Q9Y2U8 LEMD3 Inner nuclear membrane protein Man1 Q32P28 LEPRE1Prolyl 3-hydroxylase 1 O95202 LETM1 LETM1 and EF-hand domain- containingprotein 1, mit Q08380 LGALS3BP Galectin-3-binding protein Q99538 LGMNLegumain P18858 LIG1 DNA ligase 1 P38571 LIPA Lysosomal acidlipase/cholesteryl ester hydrolase P49257 LMAN1 Protein ERGIC-53 Q12907LMAN2 Vesicular integral-membrane protein VIP36 Q8WVP7 LMBR1 Limb region1 protein homolog Q68DH5 LMBRD2 LMBR1 domain-containing protein 2 Q9BU23LMF2 Lipase maturation factor 2 P02545 LMNA Prelamin-A/C P20700 LMNB1Lamin-B1 Q03252 LMNB2 Lamin-B2 Q9UIQ6 LNPEP Leucyl-cystinylaminopeptidase P36776 LONP1 Lon protease homolog, mitochondrial Q8NF37LPCAT1 Lysophosphatidylcholine acyltransferase 1 Q6P1A2 LPCAT3Lysophospholipid acyltransferase 5 Q92604 LPGAT1 Acyl-CoA:lysophosphatidylglycerol acyltransferase P42704 LRPPRC Leucine-richPPR motif- containing protein, mitocho Q8N1G4 LRRC47 Leucine-richrepeat-containing protein 47 Q96AG4 LRRC59 Leucine-richrepeat-containing protein 59 Q9UFC0 LRWD1 Leucine-rich repeat and WDrepeat-containing prote Q8ND56 LSM14A Protein LSM14 homolog A Q9BX40LSM14B Protein LSM14 homolog B P48449 LSS Lanosterol synthase P09960LTA4H Leukotriene A-4 hydrolase Q96GA3 LTV1 Protein LTV1 homolog O95232LUC7L3 Luc7-like protein 3 P07948 LYN Tyrosine-protein kinase Lyn Q9UPN3MACF1 Microtubule-actin cross-linking factor 1, isoforms P43366 MAGEB1Melanoma-associated antigen B1 O15479 MAGEB2 Melanoma-associated antigenB2 O60732 MAGEC1 Melanoma-associated antigen C1 Q9UBF1 MAGEC2Melanoma-associated antigen C2 Q9Y5V3 MAGED1 Melanoma-associated antigenD1 Q9UNF1 MAGED2 Melanoma-associated antigen D2 Q96A72 MAGOHB Proteinmago nashi homolog 2 Q9H0U3 MAGT1 Magnesium transporter protein 1 P33908MAN1A1 Mannosyl-oligosaccharide 1,2- alpha-mannosidase IA O00754 MAN2B1Lysosomal alpha-mannosidase Q9Y2E5 MAN2B2 Epididymis-specific alpha-mannosidase P46821 MAP1B Microtubule-associated protein 1B Q02750 MAP2K1Dual specificity mitogen- activated protein kinase P36507 MAP2K2 Dualspecificity mitogen- activated protein kinase P27816 MAP4Microtubule-associated protein 4 P28482 MAPK1 Mitogen-activated proteinkinase 1 P27361 MAPK3 Mitogen-activated protein kinase 3 Q15691 MAPRE1Microtubule-associated protein RP/EB family member Q15555 MAPRE2Microtubule-associated protein RP/EB family member Q9NX47 MARCH5 E3ubiquitin-protein ligase MARCH5 P56192 MARS Methionine--tRNA ligase,cytoplasmic Q96GX5 MASTL Serine/threonine-protein kinase greatwallP43243 MATR3 Matrin-3 Q7Z434 MAVS Mitochondrial antiviral-signalingprotein Q96N66 MBOAT7 Lysophospholipid acyltransferase 7 Q8IVS2 MCATMalonyl-CoA-acyl carrier protein transacylase, mit Q9HCC0 MCCC2Methylcrotonoyl-CoA carboxylase beta chain, mitoch Q8NI22 MCFD2 Multiplecoagulation factor deficiency protein 2 P49736 MCM2 DNA replicationlicensing factor MCM2 P25205 MCM3 DNA replication licensing factor MCM3P33991 MCM4 DNA replication licensing factor MCM4 P33992 MCM5 DNAreplication licensing factor MCM5 Q14566 MCM6 DNA replication licensingfactor MCM6 P33993 MCM7 DNA replication licensing factor MCM7 Q9BTE3MCMBP Mini-chromosome maintenance complex-binding protei Q9ULC4 MCTS1Malignant T-cell-amplified sequence 1 Q14676 MDC1 Mediator of DNA damagecheckpoint protein 1 P40926 MDH2 Malate dehydrogenase, mitochondrialP23368 ME2 NAD-dependent malic enzyme, mitochondrial O00470 MEIS1Homeobox protein Meisl O14770 MEIS2 Homeobox protein Meis2 Q7L2J0 MEPCE7SK snRNA methylphosphate capping enzyme Q14696 MESDC2 LDLR chaperoneMESD Q8N6R0 METTL13 Methyltransferase-like protein 13 Q9H8H3 METTL7AMethyltransferase-like protein 7A Q9GZY8 MFF Mitochondrial fissionfactor O95140 MFN2 Mitofusin-2 Q6N075 MFSD5 Major facilitatorsuperfamily domain-containing pr Q8NHS3 MFSD8 Major facilitatorsuperfamily domain-containing pr O60502 MGEA5 Bifunctional protein NCOATO14880 MGST3 Microsomal glutathione S- transferase 3 Q5JRA6 MIA3Melanoma inhibitory activity protein 3 Q9BPX6 MICU1 Calcium uptakeprotein 1, mitochondrial Q99797 MIPEP Mitochondrial intermediatepeptidase P46013 MKI67 Antigen KI-67 Q9BYG3 MKI67IP MKI67 FHAdomain-interacting nucleolar phosphoprot P55196 MLLT4 Afadin Q96EY8 MMABCob(I)yrinic acid a,c-diamide adenosyltransferase, Q8N4V1 MMGT1 Membranemagnesium transporter 1 Q96T76 MMS19 MMS19 nucleotide excision repairprotein homolog Q13724 MOGS Mannosyl-oligosaccharide glucosidase Q9UBU8MORF4L1 Mortality factor 4-like protein 1 Q15014 MORF4L2 Mortalityfactor 4-like protein 2 Q9HCE1 MOV10 Putative helicase MOV-10 O00566MPHOSPH10 U3 small nucleolar ribonucleoprotein protein MPP10 Q00013 MPP155 kDa erythrocyte membrane protein Q14168 MPP2 MAGUK p55 subfamilymember 2 Q9NZW5 MPP6 MAGUK p55 subfamily member 6 P25325 MPST3-mercaptopyruvate sulfurtransferase P39210 MPV17 Protein Mpv17 Q567V2MPV17L2 Mpv17-like protein 2 Q7Z7H8 MRPL10 39S ribosomal protein L10,mitochondrial Q13084 MRPL28 39S ribosomal protein L28, mitochondrialQ9BZE1 MRPL37 39S ribosomal protein L37, mitochondrial Q9NYK5 MRPL39 39Sribosomal protein L39, mitochondrial Q9NQ50 MRPL40 39S ribosomal proteinL40, mitochondrial Q9H9J2 MRPL44 39S ribosomal protein L44,mitochondrial Q9BRJ2 MRPL45 39S ribosomal protein L45, mitochondrialQ9H2W6 MRPL46 39S ribosomal protein L46, mitochondrial Q7Z7F7 MRPL55 39Sribosomal protein L55, mitochondrial Q9Y676 MRPS18B 28S ribosomalprotein S18b, mitochondrial P82650 MRPS22 28S ribosomal protein S22,mitochondrial Q92552 MRPS27 28S ribosomal protein S27, mitochondrialQ92665 MRPS31 28S ribosomal protein S31, mitochondrial P82673 MRPS35 28Sribosomal protein S35, mitochondrial P82933 MRPS9 28S ribosomal proteinS9, mitochondrial P43246 MSH2 DNA mismatch repair protein Msh2 P52701MSH6 DNA mismatch repair protein Msh6 O43347 MSI1 RNA-binding proteinMusashi homolog 1 Q96DH6 MSI2 RNA-binding protein Musashi homolog 2P26038 MSN Moesin Q9P289 MST4 Serine/threonine-protein kinase MST4Q9BUK6 MSTO1 Protein misato homolog 1 P00395 MT-CO1 Cytochrome c oxidasesubunit 1 P00403 MT-CO2 Cytochrome c oxidase subunit 2 P03886 MT-ND1NADH-ubiquinone oxidoreductase chain 1 P03891 MT-ND2 NADH-ubiquinoneoxidoreductase chain 2 P03905 MT-ND4 NADH-ubiquinone oxidoreductasechain 4 P03915 MT-ND5 NADH-ubiquinone oxidoreductase chain 5 O94776 MTA2Metastasis-associated protein MTA2 Q13126 MTAP S-methyl-5-thioadenosinephosphorylase Q9NZJ7 MTCH1 Mitochondrial carrier homolog 1 Q9Y6C9 MTCH2Mitochondrial carrier homolog 2 Q86UE4 MTDH Protein LYRIC Q9UDX5 MTFP1Mitochondrial fission process protein 1 P11586 MTHFD1C-1-tetrahydrofolate synthase, cytoplasmic Q6UB35 MTHFD1L MonofunctionalC1- tetrahydrofolate synthase, mitoc P13995 MTHFD2 Bifunctionalmethylenetetrahydrofolate dehydrogena P42898 MTHFRMethylenetetrahydrofolate reductase Q13505 MTX1 Metaxin-1 O75431 MTX2Metaxin-2 Q969V5 MUL1 Mitochondrial ubiquitin ligase activator of NFKB 1Q9BQG0 MYBBP1A Myb-binding protein 1A P35580 MYH10 Myosin-10 P35749MYH11 Myosin-11 P35579 MYH9 Myosin-9 O14950 MYL12B Myosin regulatorylight chain 12B P60660 MYL6 Myosin light polypeptide 6 Q96H55 MYO19Unconventional myosin-XIX P41227 NAA10 N-alpha-acetyltransferase 10Q9BXJ9 NAA15 N-alpha-acetyltransferase 15, NatA auxiliary subun Q6N069NAA16 N-alpha-acetyltransferase 16, NatA auxiliary subun Q14CX7 NAA25N-alpha-acetyltransferase 25, NatB auxiliary subun Q86UY6 NAA40N-alpha-acetyltransferase 40 Q13765 NACA Nascent polypeptide-associatedcomplex subunit alp Q4G0N4 NADKD1 NAD kinase domain- containing protein1 Q13564 NAE1 NEDD8-activating enzyme E1 regulatory subunit P54802 NAGLUAlpha-N-acetylglucosaminidase P43490 NAMPT Nicotinamidephosphoribosyltransferase P55209 NAP1L1 Nucleosome assembly protein1-like 1 Q99733 NAP1L4 Nucleosome assembly protein 1-like 4 F5HFY4NAP1L4b Nucleosome assembly protein 1-like 4 P54920 NAPA Alpha-solubleNSF attachment protein P49321 NASP Nuclear autoantigenic sperm proteinQ9H0A0 NAT10 N-acetyltransferase 10 Q15021 NCAPD2 Condensin complexsubunit 1 Q9BPX3 NCAPG Condensin complex subunit 3 Q15003 NCAPHCondensin complex subunit 2 Q09161 NCBP1 Nuclear cap-binding proteinsubunit 1 Q9UBB6 NCDN Neurochondrin Q6PIU2 NCEH1 Neutral cholesterolester hydrolase 1 Q969V3 NCLN Nicalin Q9HCD5 NCOA5 Nuclear receptorcoactivator 5 Q92542 NCSTN Nicastrin O95299 NDUFA10 NADH dehydrogenase[ubiquinone] 1 alpha subcomplex Q86Y39 NDUFA11 NADH dehydrogenase[ubiquinone] 1 alpha subcomplex Q9P0J0 NDUFA13 NADH dehydrogenase[ubiquinone] 1 alpha subcomplex O95167 NDUFA3 NADH dehydrogenase P51970NDUFA8 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex Q16795 NDUFA9NADH dehydrogenase [ubiquinone] 1 alpha subcomplex O14561 NDUFAB1 Acylcarrier protein, mitochondrial O96000 NDUFB10 NADH dehydrogenase[ubiquinone] 1 beta subcomplex O43676 NDUFB3 NADH dehydrogenase O95168NDUFB4 NADH dehydrogenase [ubiquinone] 1 beta subcomplex O95169 NDUFB8NADH dehydrogenase [ubiquinone] 1 beta subcomplex Q9Y6M9 NDUFB9 NADHdehydrogenase [ubiquinone] 1 beta subcomplex P28331 NDUFS1NADH-ubiquinone oxidoreductase 75 kDa subunit, mit O75306 NDUFS2 NADHdehydrogenase [ubiquinone] iron-sulfur protei O75489 NDUFS3 NADHdehydrogenase [ubiquinone] iron-sulfur protei O75251 NDUFS7 NADHdehydrogenase O00217 NDUFS8 NADH dehydrogenase [ubiquinone] iron-sulfurprotei P49821 NDUFV1 NADH dehydrogenase P19404 NDUFV2 NADH dehydrogenase[ubiquinone] flavoprotein 2, mi P07197 NEFM Neurofilament mediumpolypeptide Q9UMX5 NENF Neudesin Q8NBF2 NHLRC2 NHL repeat-containingprotein 2 P55769 NHP2L1 NHP2-like protein 1 Q9Y221 NIP7 60S ribosomesubunit biogenesis protein NIP7 homol Q9BPW8 NIPSNAP1 Protein NipSnaphomolog 1 O15226 NKRF NF-kappa-B-repressing factor Q9BYT8 NLNNeurolysin, mitochondrial P30419 NMT1 Glycylpeptide N-tetradecanoyltransferase 1 P40261 NNMT Nicotinamide N- methyltransferaseQ13423 NNT NAD(P) transhydrogenase, mitochondrial Q9Y3T9 NOC2L Nucleolarcomplex protein 2 homolog Q8WTT2 NOC3L Nucleolar complex protein 3homolog Q9BVI4 NOC4L Nucleolar complex protein 4 homolog Q5SY16 NOL9Polynucleotide 5-hydroxyl-kinase NOL9 Q15155 NOMO1 Nodal modulator 1Q5JPE7 NOMO2 Nodal modulator 2 P69849 NOMO3 Nodal modulator 3 Q15233NONO Non-POU domain-containing octamer-binding protein O00567 NOP56Nucleolar protein 56 Q9Y2X3 NOP58 Nucleolar protein 58 Q8IVI9 NOSTRINNostrin O15118 NPC1 Niemann-Pick C1 protein P61916 NPC2 Epididymalsecretory protein E1 P55786 NPEPPS Puromycin-sensitive aminopeptidaseP06748 NPM1 Nucleophosmin O75607 NPM3 Nucleoplasmin-3 P15559 NQO1NAD(P)H dehydrogenase [quinone] 1 P04150 NR3C1 Glucocorticoid receptorP01111 NRAS GTPase NRas O43847 NRD1 Nardilysin Q8IXM6 NRM Nurim Q15738NSDHL Sterol-4-alpha-carboxylate 3- dehydrogenase, decath P46459 NSFVesicle-fusing ATPase Q08J23 NSUN2 tRNA (cytosine(34)-C(5))-methyltransferase P49902 NT5C2 Cytosolic purine 5-nucleotidase Q9HOP0NT5C3 Cytosolic 5-nucleotidase 3 Q969T7 NT5C3L Cytosolic 5-nucleotidaseIII-like protein Q5TFE4 NT5DC1 5-nucleotidase domain- containing protein1 Q9H857 NT5DC2 5-nucleotidase domain- containing protein 2 Q86UY8NT5DC3 5-nucleotidase domain- containing protein 3 Q9BV86 NTMT1N-terminal Xaa-Pro-Lys N- methyltransferase 1 Q9BSD7 NTPCRCancer-related nucleoside- triphosphatase Q02818 NUCB1 Nucleobindin-1P80303 NUCB2 Nucleobindin-2 Q9Y266 NUDC Nuclear migration protein nudCQ96RS6 NUDCD1 NudC domain-containing protein 1 Q9BQG2 NUDT12 PeroxisomalNADH pyrophosphatase NUDT12 Q9NV35 NUDT15 Probable 8-oxo-dGTPdiphosphatase NUDT15 A8MXV4 NUDT19 Nucleoside diphosphate-linked moietyX motif 19, m O43809 NUDT21 Cleavage and polyadenylation specificityfactor su Q9BW91 NUDT9 ADP-ribose pyrophosphatase, mitochondrial Q14980NUMA1 Nuclear mitotic apparatus protein 1 P57740 NUP107 Nuclear porecomplex protein Nup107 Q8WUM0 NUP133 Nuclear pore complex protein Nup133P49790 NUP153 Nuclear pore complex protein Nup153 O75694 NUP155 Nuclearpore complex protein Nup155 Q12769 NUP160 Nuclear pore complex proteinNup160 Q92621 NUP205 Nuclear pore complex protein Nup205 Q8TEM1 NUP210Nuclear pore membrane glycoprotein 210 P35658 NUP214 Nuclear porecomplex protein Nup214 Q8NFH5 NUP35 Nucleoporin NUP53 Q8NFH4 NUP37Nucleoporin Nup37 Q8NFH3 NUP43 Nucleoporin Nup43 Q9UKX7 NUP50 Nuclearpore complex protein Nup50 Q7Z3B4 NUP54 Nucleoporin p54 P37198 NUP62Nuclear pore glycoprotein p62 Q9BW27 NUP85 Nuclear pore complex proteinNup85 Q99567 NUP88 Nuclear pore complex protein Nup88 Q8N1F7 NUP93Nuclear pore complex protein Nup93 P52948 NUP98 Nuclear pore complexprotein Nup98-Nup96 P61970 NUTF2 Nuclear transport factor 2 Q9UBU9 NXF1Nuclear RNA export factor 1 Q6DKJ4 NXN Nucleoredoxin P04181 OATOrnithine aminotransfemse, mitochondrial Q9NX40 OCIAD1 OCIAdomain-containing protein 1 Q5SWX8 ODR4 Protein odr-4 homolog Q02218OGDH 2-oxoglutarate dehydrogenase, mitochondrial O15294 OGTUDP-N-acetylglucosamine--peptide N-acetylglucosami Q9NTK5 OLA1 Obg-likeATPase 1 Q96E52 OMA1 Metalloendopeptidase OMA1, mitochondrial O60313OPA1 Dynamin-like 120 kDa protein, mitochondrial Q9H6K4 OPA3 Opticatrophy 3 protein Q9UBD5 ORC3 Origin recognition complex subunit 3P22059 OSBP Oxysterol-binding protein 1 Q9BZF1 OSBPL8 Oxysterol-bindingprotein- related protein 8 Q96SU4 OSBPL9 Oxysterol-binding protein-related protein 9 Q96FW1 OTUB1 Ubiquitin thioestemse OTUB1 Q15070 OXA1LMitochondrial inner membrane protein OXA1L P13674 P4HA1 Prolyl4-hydroxylase subunit alpha-1 P07237 P4HB Protein disulfide-isomeraseQ9UQ80 PA2G4 Proliferation-associated protein 2G4 P11940 PABPC1Polyadenylate-binding protein 1 Q9H361 PABPC3 Polyadenylate-bindingprotein 3 Q13310 PABPC4 Polyadenylate-binding protein 4 Q86U42 PABPN1Polyadenylate-binding protein 2 P68402 PAFAH1B2 Platelet-activatingfactor acetylhydrolase IB subu P22234 PAICS Multifunctional protein ADE2Q9H074 PAIP1 Polyadenylate-binding protein- interacting protein Q13177PAK2 Serine/threonine-protein kinase PAK 2 Q9NVE7 PANK4 Pantothenatekinase 4 P51003 PAPOLA Poly(A) polymerase alpha O43252 PAPSS1Bifunctional 3- phosphoadenosine 5-phosphosulfate P09874 PARP1 Poly[ADP-ribose] polymerase 1 Q96KB5 PBK Lymphokine-activated killer T-cell-originated prot Q86U86 PBRM1 Protein polybromo-1 Q15365 PCBP1Poly(rC)-binding protein 1 Q15366 PCBP2 Poly(rC)-binding protein 2P57721 PCBP3 Poly(rC)-binding protein 3 Q16822 PCK2 Phosphoenolpyruvatecarboxykinase [GTP], mitochond Q15154 PCM1 Pericentriolar material 1protein P22061 PCMT1 Protein-L-isoaspartate(D- aspartate) O-methyltransfP12004 PCNA Proliferating cell nuclear antigen Q9UHG3 PCYOX1Prenylcysteine oxidase 1 Q8NBM8 PCYOX1L Prenylcysteine oxidase-likeP49585 PCYT1A Choline-phosphate cytidylyltransferase A Q14690 PDCD11Protein RRP5 homolog Q53EL6 PDCD4 Programmed cell death protein 4 O14737PDCD5 Programmed cell death protein 5 O75340 PDCD6 Programmed cell deathprotein 6 Q8WUM4 PDCD6IP Programmed cell death 6- interacting proteinQ9H2J4 PDCL3 Phosducin-like protein 3 Q6L8Q7 PDE12 2,5-phosphodiesterase12 P08559 PDHA1 Pyruvate dehydrogenase E1 component subunit alpha,P11177 PDHB Pyruvate dehydrogenase E1 component subunit beta, P30101PDIA3 Protein disulfide-isomerase A3 P13667 PDIA4 Proteindisulfide-isomerase A4 Q15084 PDIA6 Protein disulfide-isomerase A6O00151 PDLIM1 PDZ and LIM domain protein 1 Q9P0J1 PDP1 Q9NUG6 PDRG1 p53and DNA damage-regulated protein 1 Q29RF7 PDS5A Sister chromatidcohesion protein PDS5 homolog A O00764 PDXK Pyridoxal kinase P30086PEBP1 Phosphatidylethanolamine- binding protein 1 Q9BY49 PECRPeroxisomal trans-2-enoyl-CoA reductase Q9UBV8 PEF1 Peflin Q9BRX2 PELOProtein pelota homolog Q8IZL8 PELP1 Proline-, glutamic acid- andleucine-rich protein O00541 PES1 Pescadillo homolog O96011 PEX11BPeroxisomal membrane protein 11B Q9Y5Y5 PEX16 Peroxisomal membraneprotein PEX16 P40855 PEX19 Peroxisomal biogenesis factor 19 PFAS O15067Phosphoribosylformylglycinamidine synthase Q9UHV9 PFDN2 Prefoldinsubunit 2 Q99471 PFDN5 Prefoldin subunit 5 P17858 PFKL6-phosphofructokinase, liver type P08237 PFKM 6-phosphofructokinase,muscle type Q01813 PFKP 6-phosphofructokinase type C P07737 PFN1Profilin-1 Q96HS1 PGAM5 Serine/threonine-protein phosphatase PGAM5,mitoch P00558 PGK1 Phosphoglycerate kinase 1 P07205 PGK2Phosphoglycerate kinase 2 P36871 PGM1 Phosphoglucomutase-1 O95394 PGM3Phosphoacetylglucosamine mutase O00264 PGRMC1 Membrane-associatedprogesterone receptor componen O15173 PGRMC2 Membrane-associatedprogesterone receptor componen P35232 PHB Prohibitin Q99623 PHB2Prohibitin-2 O43175 PHGDH D-3-phosphoglycerate dehydrogenase Q9BTU6PI4K2A Phosphatidylinositol 4-kinase type 2-alpha Q9UBF8 PI4KBPhosphatidylinositol 4-kinase beta Q13492 PICALMPhosphatidylinositol-binding clathrin assembly pro Q92643 PIGKGPI-anchor transamidase Q969N2 PIGT GPI transamidase component PIG-TQ9H490 PIGU Phosphatidylinositol glycan anchor biosynthesis cl Q13526PIN1 Peptidyl-prolyl cis-trans isomerase NIMA-interacti Q9UG56 PISDPhosphatidylserine decarboxylase proenzyme Q00169 PITPNAPhosphatidylinositol transfer protein alpha isofor P48739 PITPNBPhosphatidylinositol transfer protein beta isoform Q5JRX3 PITRM1Presequence protease, mitochondrial P30613 PKLR Pyruvate kinase isozymesR/L P14618 PKM Pyruvate kinase isozymes M1/M2 Q99640 PKMYT1Membrane-associated tyrosine- and threonine-specif Q16512 PKN1Serine/threonine-protein kinase N1 Q16513 PKN2 Serine/threonine-proteinkinase N2 Q9Y446 PKP3 Plakophilin-3 Q8NCC3 PLA2G15 Group XVphospholipase A2 Q8NHP8 PLBD2 Putative phospholipase B-like 2 P19174PLCG1 1-phosphatidylinositol 4,5- bisphosphate phosphodie Q8IV08 PLD3Phospholipase D3 Q15149 PLEC Plectin Q99541 PLIN2 Perilipin-2 O60664PLIN3 Perilipin-3 P53350 PLK1 Serine/threonine-protein kinase PLK1Q02809 PLOD1 Procollagen-lysine, 2- oxoglutarate 5-dioxygenase 1 P13797PLS3 Plastin-3 Q10713 PMPCA Mitochondrial-processing peptidase subunitalpha O75439 PMPCB Mitochondrial-processing peptidase subunit betaQ9H307 PNN Pinin Q96AD5 PNPLA2 Patatin-like phospholipasedomain-containing prote Q8TCS8 PNPT1 Polyribonucleotidenucleotidyltransferase 1, mitoc F8VUJ3 POC1B-GALNT4 Protein POC1B-GALNT4 Q14181 POLA2 DNA polymerase alpha subunit B P28340 POLD1 DNApolymerase delta catalytic subunit Q9Y257 POLDIP2 Polymerasedelta-interacting protein 2 P24928 POLR2A DNA-directed RNA polymerase IIsubunit RPB1 P30876 POLR2B DNA-directed RNA polymerase II subunit RPB2O00411 POLRMT DNA-directed RNA polymerase, mitochondrial Q15165 PON2Serum paraoxonase/arylesterase 2 Q99575 POP1 Ribonucleases P/MRP proteinsubunit POP1 P16435 POR NADPH--cytochrome P450 reductase Q9H2U2 PPA2Inorganic pyrophosphatase 2, mitochondrial Q9NQ55 PPAN Suppressor ofSWI4 1 homolog C9J3F9 PPAN-P2RY11 Protein PPAN-P2RY11 Q06203 PPATAmidophosphoribosyltransferase Q13356 PPIL2 Peptidyl-prolyl cis-transisomerase-like 2 P49593 PPM1F Protein phosphatase 1F O15355 PPM1GProtein phosphatase 1G Q9Y570 PPME1 Protein phosphatase methylesterase 1P62136 PPP1CA Serine/threonine-protein phosphatase PP1-alpha cat P62140PPP1CB Serine/threonine-protein phosphatase PP1-beta cata P36873 PPP1CCSerine/threonine-protein phosphatase PP1-gamma cat P67775 PPP2CASerine/threonine-protein phosphatase 2A catalytic P62714 PPP2CBSerine/threonine-protein phosphatase 2A catalytic P30153 PPP2R1ASerine/threonine-protein phosphatase 2A 65 kDa reg P30154 PPP2R1BSerine/threonine-protein phosphatase 2A 65 kDa reg P63151 PPP2R2ASerine/threonine-protein phosphatase 2A 55 kDa reg Q15172 PPP2R5ASerine/threonine-protein phosphatase 2A 56 kDa reg Q13362 PPP2R5CSerine/threonine-protein phosphatase 2A 56 kDa reg Q14738 PPP2R5DSerine/threonine-protein phosphatase 2A 56 kDa reg P60510 PPP4CSerine/threonine-protein phosphatase 4 catalytic s O00743 PPP6CSerine/threonine-protein phosphatase 6 catalytic s Q9UPN7 PPP6R1Serine/threonine-protein phosphatase 6 regulatory Q5H9R7 PPP6R3Serine/threonine-protein phosphatase 6 regulatory P50897 PPT1Palmitoyl-protein thioesterase 1 Q9UMR5 PPT2 Lysosomal thioesterase PPT2O43663 PRC1 Protein regulator of cytokinesis 1 P42785 PRCP LysosomalPro-X carboxypeptidase Q06830 PRDX1 Peroxiredoxin-1 P32119 PRDX2Peroxiredoxin-2 P30048 PRDX3 Thioredoxin-dependent peroxide reductase,mitochon Q13162 PRDX4 Peroxiredoxin-4 P30044 PRDX5 Peroxiredoxin-5,mitochondrial P30041 PRDX6 Peroxiredoxin-6 Q9HCU5 PREB Prolactinregulatory element- binding protein P48147 PREP Prolyl endopeptidaseQ4J6C6 PREPL Prolyl endopeptidase-like P49643 PRIM2 DNA primase largesubunit P17612 PRKACA cAMP-dependent protein kinase catalytic subunit a1P54619 PRKAG1 5-AMP-activated protein kinase subunit gamma-1 P10644PRKAR1A cAMP-dependent protein kinase type I-alpha regulat P13861PRKAR2A cAMP-dependent protein kinase type II-alpha regula P31323PRKAR2B cAMP-dependent protein kinase type II-beta regulat P05771 PRKCBProtein kinase C beta type P14314 PRKCSH Glucosidase 2 subunit betaP78527 PRKDC DNA-dependent protein kinase catalytic subunit O75569 PRKRAInterferon-inducible double stranded RNA-dependent Q99873 PRMT1 Proteinarginine N- methyltransferase 1 O60678 PRMT3 Protein arginine N-methyltransferase 3 O14744 PRMT5 Protein arginine N- methyltransferase 5Q9UMS4 PRPF19 Pre-mRNA-processing factor 19 Q5VTL8 PRPF38BPre-mRNA-splicing factor 38B O75400 PRPF40A Pre-mRNA-processing factor40 homolog A O94906 PRPF6 Pre-mRNA-processing factor 6 Q6P2Q9 PRPF8Pre-mRNA-processing-splicing factor 8 P48634 PRRC2A Protein PRRC2AQ9Y520 PRRC2C Protein PRRC2C P07602 PSAP Proactivator polypeptide P49768PSEN1 Presenilin-1 P49810 PSEN2 Presenilin-2 O75475 PSIP1 PC4 andSFRS1-interacting protein P25786 PSMA1 Proteasome subunit alpha type-1P25787 PSMA2 Proteasome subunit alpha type-2 P25788 PSMA3 Proteasomesubunit alpha type-3 P25789 PSMA4 Proteasome subunit alpha type-4 P28066PSMA5 Proteasome subunit alpha type-5 P60900 PSMA6 Proteasome subunitalpha type-6 O14818 PSMA7 Proteasome subunit alpha type-7 P20618 PSMB1Proteasome subunit beta type-1 P49721 PSMB2 Proteasome subunit betatype-2 P49720 PSMB3 Proteasome subunit beta type-3 P28070 PSMB4Proteasome subunit beta type-4 P28074 PSMB5 Proteasome subunit betatype-5 P28072 PSMB6 Proteasome subunit beta type-6 Q99436 PSMB7Proteasome subunit beta type-7 P62191 PSMC1 26S protease regulatorysubunit 4 P35998 PSMC2 26S protease regulatory subunit 7 P17980 PSMC326S protease regulatory subunit 6A P43686 PSMC4 26S protease regulatorysubunit 6B P62195 PSMC5 26S protease regulatory subunit 8 P62333 PSMC626S protease regulatory subunit 10B Q99460 PSMD1 26S proteasomenon-ATPase regulatory subunit 1 O75832 PSMD10 26S proteasome non-ATPaseregulatory subunit 10 O00231 PSMD11 26S proteasome non-ATPase regulatorysubunit 11 Q9UNM6 PSMD13 26S proteasome non-ATPase regulatory subunit 13O00487 PSMD14 26S proteasome non-ATPase regulatory subunit 14 Q13200PSMD2 26S proteasome non-ATPase regulatory subunit 2 O43242 PSMD3 26Sproteasome non-ATPase regulatory subunit 3 Q16401 PSMD5 26S proteasomenon-ATPase regulatory subunit 5 Q15008 PSMD6 26S proteasome non-ATPaseregulatory subunit 6 P51665 PSMD7 26S proteasome non-ATPase regulatorysubunit 7 P48556 PSMD8 26S proteasome non-ATPase regulatory subunit 8Q06323 PSME1 Proteasome activator complex subunit 1 Q9UL46 PSME2Proteasome activator complex subunit 2 P61289 PSME3 Proteasome activatorcomplex subunit 3 Q92530 PSMF1 Proteasome inhibitor PI31 subunit O95456PSMG1 Proteasome assembly chaperone 1 Q8WXF1 PSPC1 Paraspeckle component1 P26599 PTBP1 Polypyrimidine tract-binding protein 1 O95758 PTBP3Polypyrimidine tract-binding protein 3 Q96EY7 PTCD3 Pentatricopeptiderepeat- containing protein 3, mit P48651 PTDSS1 Phosphatidylserinesynthase 1 Q9BVG9 PTDSS2 Phosphatidylserine synthase 2 Q9H7Z7 PTGES2Prostaglandin E synthase 2 Q15185 PTGES3 Prostaglandin E synthase 3Q8N8N7 PTGR2 Prostaglandin reductase 2 Q9P035 PTPLAD1 3-hydroxyacyl-CoAdehydratase 3 P18031 PTPN1 Tyrosine-protein phosphatase non-receptortype 1 Q06124 PTPN11 Tyrosine-protein phosphatase non-receptor type 11Q9H3S7 PTPN23 Tyrosine-protein phosphatase non-receptor type 23 Q6NZI2PTRF Polymerase I and transcript release factor Q9Y3E5 PTRH2Peptidyl-tRNA hydrolase 2, mitochondrial Q9UHX1 PUF60Poly(U)-binding-splicing factor PUF60 Q14671 PUM1 Pumilio homolog 1Q96PZ0 PUS7 Pseudouridylate synthase 7 homolog Q15269 PWP2 Periodictryptophan protein 2 homolog Q9NR77 PXMP2 Peroxisomal membrane protein 2P32322 PYCR1 Pyrroline-5-carboxylate reductase 1, mitochondrial Q96C36PYCR2 Pyrroline-5-carboxylate reductase 2 P11216 PYGB Glycogenphosphorylase, brain form P06737 PYGL Glycogen phosphorylase, liver formP20742 PZP Pregnancy zone protein Q5XKP0 QIL1 Protein QIL1 Q96PU8 QKIProtein quaking P61026 RAB10 Ras-related protein Rab-10 P62491 RAB11ARas-related protein Rab-11A Q15907 RAB11B Ras-related protein Rab-11BP61106 RAB14 Ras-related protein Rab-14 Q9NP72 RAB18 Ras-related proteinRab-18 P62820 RAB1A Ras-related protein Rab-1A Q9H0U4 RAB1B Ras-relatedprotein Rab-1B Q9UL25 RAB21 Ras-related protein Rab-21 Q969Q5 RAB24Ras-related protein Rab-24 P61019 RAB2A Ras-related protein Rab-2AQ8WUD1 RAB2B Ras-related protein Rab-2B Q15042 RAB3GAP1 Rab3GTPase-activating protein catalytic subunit Q9H2M9 RAB3GAP2 Rab3GTPase-activating protein non-catalytic subun Q8TBN0 RAB3IL1 Guaninenucleotide exchange factor for Rab-3A P20339 RAB5A Ras-related proteinRab-5A P61020 RAB5B Ras-related protein Rab-5B P51148 RAB5C Ras-relatedprotein Rab-5C P51149 RAB7A Ras-related protein Rab-7a P51151 RAB9ARas-related protein Rab-9A Q7Z6M1 RABEPK Rab9 effector protein withkelch motifs P54727 RAD23B UV excision repair protein RAD23 homolog BQ92878 RAD50 DNA repair protein RAD50 P78406 RAE1 mRNA export factorP11233 RALA Ras-related protein Ral-A Q9UKM9 RALY RNA-binding proteinRaly P62826 RAN GTP-binding nuclear protein Ran P43487 RANBP1Ran-specific GTPase-activating protein P49792 RANBP2 E3 SUMO-proteinligase RanBP2 P62834 RAP1A Ras-related protein Rap-1A P61224 RAP1BRas-related protein Rap-1b P61225 RAP2B Ras-related protein Rap-2bQ9Y3L5 RAP2C Ras-related protein Rap-2c P54136 RARS Arginine--tRNAligase, cytoplasmic Q8IY67 RAVER1 Ribonucleoprotein PTB- binding 1Q09028 RBBP4 Histone-binding protein RBBP4 Q16576 RBBP7 Histone-bindingprotein RBBP7 Q9NWB1 RBFOX1 RNA binding protein fox-1 homolog 1 O43251RBFOX2 RNA binding protein fox-1 homolog 2 P98175 RBM10 RNA-bindingprotein 10 Q8IXT5 RBM12B RNA-binding protein 12B Q96PK6 RBM14RNA-binding protein 14 B0LM41 RBM14/RBM4 Protein RBM14-RBM4 Q96T37 RBM15Putative RNA-binding protein 15 P49756 RBM25 RNA-binding protein 25Q9NW13 RBM28 RNA-binding protein 28 P98179 RBM3 Putative RNA-bindingprotein 3 Q14498 RBM39 RNA-binding protein 39 Q9BWF3 RBM4 RNA-bindingprotein 4 Q9BQ04 RBM4B RNA-binding protein 4B P29558 RBMS1 RNA-bindingmotif, single- stranded-interacting pro P38159 RBMX RNA-binding motifprotein, X chromosome Q96E39 RBMXL1 RNA binding motif protein, X-linked-like-1 Q15293 RCN1 Reticulocalbin-1 Q14257 RCN2 Reticulocalbin-2Q8TC12 RDH11 Retinol dehydrogenase 11 Q8NBN7 RDH13 Retinol dehydrogenase13 Q9HBH5 RDH14 Retinol dehydrogenase 14 P35241 RDX Radixin P46063 RECQLATP-dependent DNA helicase Q1 Q00765 REEP5 Receptor expression-enhancingprotein 5 O15258 RER1 Protein RER1 Q6NUM9 RETSAT All-trans-retinol13,14- reductase P35250 RFC2 Replication factor C subunit 2 P40938 RFC3Replication factor C subunit 3 P35249 RFC4 Replication factor C subunit4 P40937 RFC5 Replication factor C subunit 5 Q96AA3 RFT1 Protein RFT1homolog Q15382 RHEB GTP-binding protein Rheb P61586 RHOA Transformingprotein RhoA P08134 RHOC Rho-related GTP-binding protein RhoC Q8IXI1RHOT2 Mitochondrial Rho GTPase 2 Q5UIP0 RIF1 Telomere-associated proteinRIF1 Q6NUQ1 RINT1 RAD50-interacting protein 1 Q9BVS4 RIOK2Serine/threonine-protein kinase RIO2 O43353 RIPK2 Receptor-interactingserine/threonine-protein kina Q9NWS8 RMND1 Required for meiotic nucleardivision protein 1 ho O00584 RNASET2 Ribonuclease T2 Q9H920 RNF121 RINGfinger protein 121 Q9UBS8 RNF14 E3 ubiquitin-protein ligase RNF14 Q5VTR2RNF20 E3 ubiquitin-protein ligase BRE1A Q9H4A4 RNPEP Aminopeptidase BP27694 RPA1 Replication protein A 70 kDa DNA-binding subunit P15927 RPA2Replication protein A 32 kDa subunit P62906 RPL10A 60S ribosomal proteinL10a Q02543 RPL18A 60S ribosomal protein L18a P62750 RPL23 A 60Sribosomal protein L23a P61254 RPL26 60S ribosomal protein L26 P62888RPL30 60S ribosomal protein L30 P36578 RPL4 60S ribosomal protein L4P18124 RPL7 60S ribosomal protein L7 P62424 RPL7A 60S ribosomal proteinL7a Q6DKI1 RPL7L1 60S ribosomal protein L7-like 1 P62917 RPL8 60Sribosomal protein L8 P05387 RPLP2 60S acidic ribosomal protein P2 P04843RPN1 Dolichyl- diphosphooligosaccharide-protein glycosy P04844 RPN2Dolichyl- diphosphooligosaccharide-protein glycosy Q9NQG5 RPRD1BRegulation of nuclear pre- mRNA domain-containing p P46783 RPS10 40Sribosomal protein S10 P62277 RPS13 40S ribosomal protein S13 P62244RPS15A 40S ribosomal protein S15a P62249 RPS16 40S ribosomal protein S16P62269 RPS18 40S ribosomal protein S18 P15880 RPS2 40S ribosomal proteinS2 P62266 RPS23 40S ribosomal protein S23 P62847 RPS24 40S ribosomalprotein S24 P62979 RPS27A Ubiquitin-40S ribosomal protein S27a P23396RPS3 40S ribosomal protein S3 P61247 RPS3A 40S ribosomal protein S3aQ15418 RPS6KA1 Ribosomal protein S6 kinase alpha-1 Q15349 RPS6KA2Ribosomal protein S6 kinase alpha-2 P51812 RPS6KA3 Ribosomal protein S6kinase alpha-3 P62241 RPS8 40S ribosomal protein S8 A6NE09 RPSAP58Protein RPSAP58 Q8IZ73 RPUSD2 RNA pseudouridylate synthasedomain-containing pro Q9HB90 RRAGC Ras-related GTP-binding protein CQ9P2E9 RRBP1 Ribosome-binding protein 1 P23921 RRM1Ribonucleoside-diphosphate reductase large subunit P31350 RRM2Ribonucleoside-diphosphate reductase subunit M2 P56182 RRP1 RibosomalRNA processing protein 1 homolog A Q5JTH9 RRP12 RRP12-like proteinQ14684 RRP1B Ribosomal RNA processing protein 1 homolog B O76021 RSL1D1Ribosomal L1 domain- containing protein 1 Q92541 RTF1 RNApolymerase-associated protein RTF1 homolog O95197 RTN3 Reticulon-3Q9NQC3 RTN4 Reticulon-4 Q8WWV3 RTN4IP1 Reticulon-4-interacting protein1, mitochondrial Q9Y265 RUVBL1 RuvB-like 1 Q9Y230 RUVBL2 RuvB-like 2Q9NTJ5 SACM1L Phosphatidylinositide phosphatase SAC1 Q15424 SAFBScaffold attachment factor B1 Q14151 SAFB2 Scaffold attachment factor B2Q9Y512 SAMM50 Sorting and assembly machinery component 50 homolo Q9NSI8SAMSN1 SAM domain-containing protein SAMSN-1 Q9NR31 SAR1A GTP-bindingprotein SAR1a Q9Y6B6 SAR1B GTP-binding protein SAR1b P49591 SARSSerine--tRNA ligase, cytoplasmic Q9NP81 SARS2 Serine--tRNA ligase,mitochondrial O43290 SART1 U4/U6.U5 tri-snRNP-associated protein 1Q15020 SART3 Squamous cell carcinoma antigen recognized by T-ce O14828SCAMP3 Secretory carrier-associated membrane protein 3 Q8WTV0 SCARB1Scavenger receptor class B member 1 Q14108 SCARB2 Lysosome membraneprotein 2 Q8NBX0 SCCPDH Saccharopine dehydrogenase- like oxidoreductaseO00767 SCD Acyl-CoA desaturase Q8WVM8 SCFD1 Sec1 familydomain-containing protein 1 O75880 SCO1 Protein SCO1 homolog,mitochondrial O43819 SCO2 Protein SCO2 homolog, mitochondrial P22307SCP2 Non-specific lipid-transfer protein Q9HB40 SCPEP1Retinoid-inducible serine carboxypeptidase O00560 SDCBP Syntenin-1Q9BRK5 SDF4 45 kDa calcium-binding protein P31040 SDHA Succinatedehydrogenase [ubiquinone] flavoprotein P21912 SDHB Succinatedehydrogenase [ubiquinone] iron-sulfur s P67812 SEC11A Signal peptidasecomplex catalytic subunit SEC11A P55735 SEC13 Protein SEC13 homologO15027 SEC16A Protein transport protein Sec16A O75396 SEC22BVesicle-trafficking protein SEC22b Q15436 SEC23A Protein transportprotein Sec23A Q15437 SEC23B Protein transport protein Sec23B Q9Y6Y8SEC23IP 5EC23-interacting protein P53992 SEC24C Protein transportprotein Sec24C O94979 SEC31A Protein transport protein Sec31A P61619SEC61A1 Protein transport protein Sec61 subunit alpha isof Q99442 SEC62Translocation protein SEC62 Q9UGP8 SEC63 Translocation protein SEC63homolog Q9UBV2 SEL1L Protein sel-1 homolog 1 Q15019 SEPT2 Septin-2Q16181 SEPT7 Septin-7 Q8NC51 SERBP1 Plasminogen activator inhibitor 1RNA-binding prot P30740 SERPINB1 Leukocyte elastase inhibitor P29508SERPINB3 Serpin B3 P35237 SERPINB6 Serpin B6 P50454 SERPINH1 Serpin H1P58004 SESN2 Sestrin-2 Q01105 SET Protein SET Q15637 SF1 Splicing factor1 Q15459 SF3A1 Splicing factor 3A subunit 1 Q12874 SF3A3 Splicing factor3A subunit 3 O75533 SF3B1 Splicing factor 3B subunit 1 Q13435 SF3B2Splicing factor 3B subunit 2 Q9BWJ5 SF3B5 Splicing factor 3B subunit 5P23246 SFPQ Splicing factor, proline- and glutamine-rich Q9H9B4 SFXN1Sideroflexin-1 Q96NB2 SFXN2 Sideroflexin-2 Q6P4A7 SFXN4 Sideroflexin-4O95470 SGPL1 Sphingosine-1-phosphate lyase 1 O43765 SGTA Smallglutamine-rich tetratricopeptide repeat-cont Q99961 SH3GL1 Endophilin-A2Q9Y371 SH3GLB1 Endophilin-B1 P34896 SHMT1 Serinehydroxymethyltransferase, cytosolic P34897 SHMT2 Serinehydroxymethyltransferase, mitochondrial Q9HAT2 SIAE SialateO-acetylesterase Q99720 SIGMAR1 Sigma non-opioid intracellular receptor1 Q96ST3 SIN3A Paired amphipathic helix protein Sin3a P42285 SKIV2L2Superkiller viralicidic activity 2-like 2 P63208 SKP1 S-phasekinase-associated protein 1 P41440 SLC19A1 Folate transporter 1 P43007SLC1A4 Neutral amino acid transporter A Q15758 SLC1A5 Neutral amino acidtransporter B(0) P53007 SLC25A1 Tricarboxylate transport protein,mitochondrial Q9UBX3 SLC25A10 Mitochondrial dicarboxylate carrier Q02978SLC25A11 Mitochondrial 2- oxoglutarate/malate carrier protei O75746SLC25A12 Calcium-binding mitochondrial carrier protein Aral Q9UJS0SLC25A13 Calcium-binding mitochondrial carrier protein Aral Q9Y619SLC25A15 Mitochondrial ornithine transporter 1 P16260 SLC25A16 Gravesdisease carrier protein Q9HC21 SLC25A19 Mitochondrial thiaminepyrophosphate carrier O43772 SLC25A20 Mitochondrialcarnitine/acylcarnitine carrier prot Q9H936 SLC25A22 Mitochondrialglutamate carrier 1 Q6NUK1 SLC25A24 Calcium-binding mitochondrialcarrier protein SCaM Q70HW3 SLC25A26 S-adenosylmethionine mitochondrialcarrier protein Q00325 SLC25A3 Phosphate carrier protein, mitochondrialQ5SVS4 SLC25A30 Kidney mitochondrial carrier protein 1 Q9H2D1 SLC25A32Mitochondrial folate transporter/carrier Q9BSK2 SLC25A33 Solute carrierfamily 25 member 33 P12235 SLC25A4 ADP/ATP translocase 1 Q8TBP6 SLC25A40Solute carrier family 25 member 40 P05141 SLC25A5 ADP/ATP translocase 2P12236 SLC25A6 ADP/ATP translocase 3 O14975 SLC27A2 Very long-chainacyl-CoA synthetase P11166 SLC2A1 Solute carrier family 2, facilitatedglucose trans Q8TAD4 SLC30A5 Zinc transporter 5 Q6NXT4 SLC30A6 Zinctransporter 6 Q8NEW0 SLC30A7 Zinc transporter 7 Q6PML9 SLC30A9 Zinctransporter 9 O00400 SLC33A1 Acetyl-coenzyme A transporter 1 Q8TB61SLC35B2 Adenosine 3-phospho 5- phosphosulfate transporter Q8IXU6 SLC35F2Solute carrier family 35 member F2 Q96QD8 SLC38A2 Sodium-coupled neutralamino acid transporter 2 P08195 SLC3A2 4F2 cell-surface antigen heavychain P30825 SLC7A1 High affinity cationic amino acid transporter 1Q9H2G2 SLK STE20-like serine/threonine-protein kinase Q8WU79 SMAP2Stromal membrane-associated protein 2 P28370 SMARCA1 Probable globaltranscription activator SNF2L1 P51532 SMARCA4 Transcription activatorBRG1 O60264 SMARCA5 SWI/SNF-related matrix- associated actin-dependentQ12824 SMARCB1 SWI/SNF-related matrix- associated actin-dependent Q92922SMARCC1 SWI/SNF complex subunit SMARCC1 Q14683 SMC1A Structuralmaintenance of chromosomes protein 1A O95347 SMC2 Structural maintenanceof chromosomes protein 2 Q9UQE7 SMC3 Structural maintenance ofchromosomes protein 3 Q9NTJ3 SMC4 Structural maintenance of chromosomesprotein 4 A6NHR9 SMCHD1 Structural maintenance of chromosomes flexiblehin Q16637 SMN1 Survival motor neuron protein P17405 SMPD1 Sphingomyelinphosphodiesterase Q9NXE4 SMPD4 Sphingomyelin phosphodiesterase 4 Q2TAY7SMU1 WD40 repeat-containing protein SMU1 Q9H7B4 SMYD3 SET and MYNDdomain- containing protein 3 O00161 SNAP23 Synaptosomal-associatedprotein 23 O95721 SNAP29 Synaptosomal-associated protein 29 Q7KZF4 SND1Staphylococcal nuclease domain- containing protein O75643 SNRNP200 U5small nuclear ribonucleoprotein 200 kDa helicas Q96DI7 SNRNP40 U5 smallnuclear ribonucleoprotein 40 kDa protein P08621 SNRNP70 U1 small nuclearribonucleoprotein 70 kDa P09012 SNRPA U1 small nuclear ribonucleoproteinA P62314 SNRPD1 Small nuclear ribonucleoprotein Sm D1 Q13573 SNW1 SNWdomain-containing protein 1 Q13596 SNX1 Sorting nexin-1 O60749 SNX2Sorting nexin-2 Q96L92 SNX27 Sorting nexin-27 Q9Y5X3 SNX5 Sortingnexin-5 Q9UNH7 SNX6 Sorting nexin-6 Q9Y5X1 SNX9 Sorting nexin-9 P35610SOAT1 Sterol O-acyltransferase 1 P04179 SOD2 Superoxide dismutase P18583SON Protein SON Q99523 SORT1 Sortilin O60271 SPAG9 C-Jun-amino-terminalkinase- interacting protein 4 Q8NB90 SPATA5 Spermatogenesis-associatedprotein 5 Q8NBT2 SPC24 Kinetochore protein Spc24 Q9HBM1 SPC25Kinetochore protein Spc25 Q15005 SPCS2 Signal peptidase complex subunit2 Q8N0X7 SPG20 Spartin Q9H2V7 SPNS1 Protein spinster homolog 1 P35270SPR Sepiapterin reductase P02549 SPTA1 Spectrin alpha chain,erythrocytic 1 Q13813 SPTAN1 Spectrin alpha chain, non- erythrocytic 1Q01082 SPTBN1 Spectrin beta chain, non- erythrocytic 1 O15269 SPTLC1Serine palmitoyltransferase 1 O15270 SPTLC2 Serine palmitoyltransferase2 Q14534 SQLE Squalene monooxygenase P30626 SRI Sorcin P19623 SRMSpermidine synthase P61011 SRP54 Signal recognition particle 54 kDaprotein Q9UHB9 SRP68 Signal recognition particle 68 kDa protein O76094SRP72 Signal recognition particle 72 kDa protein Q965B4 SRPK1 SRSFprotein kinase 1 P08240 SRPR Signal recognition particle receptorsubunit alpha Q9Y5M8 SRPRB Signal recognition particle receptor subunitbeta Q9UQ35 SRRM2 Serine/arginine repetitive matrix protein 2 Q9BXP5SRRT Serrate RNA effector molecule homolog O75494 SRSF10Serine/arginine-rich splicing factor 10 P84103 SRSF3Serine/arginine-rich splicing factor 3 Q16629 SRSF7 Serine/arginine-richsplicing factor 7 Q13242 SRSF9 Serine/arginine-rich splicing factor 9Q04837 SSBP1 Single-stranded DNA-binding protein, mitochondrial P43307SSR1 Translocon-associated protein subunit alpha P51571 SSR4Translocon-associated protein subunit delta Q08945 SSRP1 FACT complexsubunit SSRP1 P50502 ST13 Hsc70-interacting protein Q8N3U4 STAG2 Cohesinsubunit SA-2 Q92783 STAM Signal transducing adapter molecule 1 O95772STARD3NL MLN64 N-terminal domain homolog Q9NQZ5 STARD7 StAR-relatedlipid transfer protein 7, mitochondri P42224 STAT1 Signal transducer andactivator of transcription 1 P52630 STAT2 Signal transducer andactivator of transcription 2 P40763 STAT3 Signal transducer andactivator of transcription 3 P42229 STAT5A Signal transducer andactivator of transcription 5 P51692 STAT5B Signal transducer andactivator of transcription 5 O95793 STAU1 Double-stranded RNA-bindingprotein Staufen homolo Q13586 STIM1 Stromal interaction molecule 1P31948 STIP1 Stress-induced-phosphoprotein 1 Q9Y6E0 STK24Serine/threonine-protein kinase 24 Q13188 STK3 Serine/threonine-proteinkinase 3 Q13043 STK4 Serine/threonine-protein kinase 4 P16949 STMN1Stathmin Q9UJZ1 STOML2 Stomatin-like protein 2 Q9Y3F4 STRAPSerine-threonine kinase receptor- associated protei Q96519 STRBPSpermatid perinuclear RNA- binding protein P46977 STT3A Dolichyl-diphosphooligosaccharide--protein glycosy Q8TCJ2 STT3B Dolichyl-diphosphooligosaccharide--protein glycosy Q9UNE7 STUB1 E3ubiquitin-protein ligase CHIP O60499 STX10 Syntaxin-10 Q86Y82 STX12Syntaxin-12 Q9P2W9 STX18 Syntaxin-18 Q13190 STX5 Syntaxin-5 O43752 STX6Syntaxin-6 Q15833 STXBP2 Syntaxin-binding protein 2 O00186 STXBP3Syntaxin-binding protein 3 Q96I99 SUCLG2 Succinyl-CoA ligase [GDP-forming] subunit beta, mi Q8IWZ8 SUGP1 SURP and G-patch domain-containing protein 1 O94901 SUN1 SUN domain-containing protein 1 Q9UH99SUN2 SUN domain-containing protein 2 Q9Y5B9 SUPT16H FACT complex subunitSPT16 O00267 SUPT5H Transcription elongation factor SPT5 Q7KZ85 SUPT6HTranscription elongation factor SPT6 O15260 SURF4 Surfeit locus protein4 Q15022 SUZ12 Polycomb protein SUZ12 Q96A49 SYAP1 Synapse-associatedprotein 1 Q92797 SYMPK Symplekin O60506 SYNCRIP Heterogeneous nuclearribonucleoprotein Q Q9Y6A5 TACC3 Transforming acidic coiled-coil-containing protein Q9BSH4 TACO1 Translational activator of cytochrome coxidase 1 Q92804 TAF15 TATA-binding protein-associated factor 2N P37802TAGLN2 Transgelin-2 Q13148 TARDBP TAR DNA-binding protein 43 P26639 TARSThreonine--tRNA ligase, cytoplasmic Q9BW92 TARS2 Threonine--tRNA ligase,mitochondrial Q8TC07 TBC1D15 TBC1 domain family member 15 Q99426 TBCBTubulin-folding cofactor B Q9BTW9 TBCD Tubulin-specific chaperone DQ15813 TBCE Tubulin-specific chaperone E Q9Y4P3 TBL2 Transducinbeta-like protein 2 Q12788 TBL3 Transducin beta-like protein 3 Q969Z0TBRG4 Protein TBRG4 P23193 TCEA1 Transcription elongation factor Aprotein 1 Q13428 TCOF1 Treacle protein P17987 TCP1 T-complex protein 1subunit alpha Q9Y2W6 TDRKH Tudor and KH domain- containing proteinQ9NZ01 TECR Trans-2,3-enoyl-CoA reductase Q9Y4R8 TELO2 Telomere lengthregulation protein TEL2 homolog Q9NXF1 TEX10 Testis-expressed sequence10 protein Q00059 TFAM Transcription factor A, mitochondrial Q92734 TFGProtein TFG P02786 TFRC Transferrin receptor protein 1 P21980 TGM2Protein-glutamine gamma- glutamyltransferase 2 Q08188 TGM3Protein-glutamine gamma- glutamyltransferase E Q96RS0 TGS1Trimethylguanosine synthase Q8IXH7 TH1L Negative elongation factor C/DQ96FV9 THOC1 THO complex subunit 1 Q96J01 THOC3 THO complex subunit 3P52888 THOP1 Thimet oligopeptidase Q9Y2W1 THRAP3 Thyroid hormonereceptor- associated protein 3 Q9BV44 THUMPD3 THUMP domain-containingprotein 3 P31483 TIA1 Nucleolysin TIA-1 isoform p40 Q01085 TIAL1Nucleolysin TIAR P62072 TIMM10 Mitochondrial import inner membranetranslocase su Q9Y5L4 TIMM13 Mitochondrial import inner membranetranslocase su Q99595 TIMM17A Mitochondrial import inner membranetranslocase su O60830 TIMM17B Mitochondrial import inner membranetranslocase su O14925 TIMM23 Mitochondrial import inner membranetranslocase su Q5SRD1 TIMM23B Putative mitochondrial import innermembrane trans O43615 TIMM44 Mitochondrial import inner membranetranslocase su Q3ZCQ8 TIMM50 Mitochondrial import inner membranetranslocase su Q9NPL8 TIMMDC1 Translocase of inner mitochondrial membmnedomain O75663 TIPRL TIP41-like protein Q6JUT2 TIRAP3 TIRdomain-containing adapter molecule 2 Q86UE8 TLK2Serine/threonine-protein kinase tousled-like 2 E9PSI1 TM9SF1Transmembrane 9 superfamily member 1 Q99805 TM9SF2 Transmembrane 9superfamily member 2 Q9HD45 TM9SF3 Transmembrane 9 superfamily member 3Q92544 TM9SF4 Transmembrane 9 superfamily member 4 P55061 TMBIM6 Baxinhibitor 1 Q9UM00 TMCO1 Transmembrane and coiled-coil domain-containingpr Q13445 TMED1 Transmembrane emp24 domain- containing protein 1 P49755TMED10 Transmembrane emp24 domain-containing protein 10 Q15363 TMED2Transmembrane emp24 domain- containing protein 2 Q9Y3A6 TMED5Transmembrane emp24 domain- containing protein 5 Q9Y3B3 TMED7Transmembrane emp24 domain- containing protein 7 Q9BVK6 TMED9Transmembrane emp24 domain- containing protein 9 Q9H061 TMEM126ATransmembrane protein 126A Q8IUX1 TMEM126B Transmembrane protein 126BQ9P0S9 TMEM14C Transmembrane protein 14C Q9NX00 TMEM160 Transmembraneprotein 160 Q9NX61 TMEM161A Transmembrane protein 161A Q9HC07 TMEM165Transmembrane protein 165 Q86WV6 TMEM173 Transmembrane protein 173O14524 TMEM194A Transmembrane protein 194A Q8N511 TMEM199 Transmembraneprotein 199 Q6UW68 TMEM205 Transmembrane protein 205 Q9H813 TMEM206Transmembrane protein 206 Q96SK2 TMEM209 Transmembrane protein 209Q6NUQ4 TMEM214 Transmembrane protein 214 P57088 TMEM33 Transmembraneprotein 33 Q9NVV0 TMEM38B Trimeric intracellular cation channel type BQ9BTV4 TMEM43 Transmembrane protein 43 Q9BTX1 TMEM48 Nucleoporin NDC1Q9BXS4 TMEM59 Transmembrane protein 59 Q6PI78 TMEM65 Transmembraneprotein 65 Q96MH6 TMEM68 Transmembrane protein 68 Q9BUB7 TMEM70Transmembrane protein 70, mitochondrial Q8NBN3 TMEM87A Transmembraneprotein 87A Q5BJF2 TMEM97 Transmembrane protein 97 P28289 TMOD1Tropomodulin-1 Q9NYL9 TMOD3 Tropomodulin-3 P42166 TMPO Lamina-associatedpolypeptide 2, isoform alpha P42167 TMPO Lamina-associated polypeptide2, isoforms beta/gam Q6ZXV5 TMTC3 Transmembrane and TPR repeat-containing protein 3 Q9H3N1 TMX1 Thioredoxin-related transmembraneprotein 1 Q96JJ7 TMX3 Protein disulfide-isomerase TMX3 Q9H1E5 TMX4Thioredoxin-related transmembrane protein 4 Q9C0C2 TNKS1BP1 182 kDatankyrase-1-binding protein Q92973 TNPO1 Transportin-1 O14787 TNPO2Transportin-2 Q9Y5L0 TNPO3 Transportin-3 O60784 TOM1 Target of Mybprotein 1 Q9NS69 TOMM22 Mitochondrial import receptor subunit TOM22homolo O96008 TOMM40 Mitochondrial import receptor subunit TOM40 homoloO94826 TOMM70A Mitochondrial import receptor subunit TOM70 P11388 TOP2ADNA topoisomerase 2-alpha Q02880 TOP2B DNA topoisomerase 2-beta O14656TOR1A Torsin-1A Q5JTV8 TOR1AIP1 Torsin-1A-interacting protein 1 P04637TP53 Cellular tumor antigen p53 O43399 TPD52L2 Tumor protein D54 P06753TPM3 Tropomyosin alpha-3 chain P67936 TPM4 Tropomyosin alpha-4 chainO14773 TPP1 Tripeptidyl-peptidase 1 P12270 TPR Nucleoprotein TPR P13693TPT1 Tmnslationally-controlled tumor protein Q9ULW0 TPX2 Targetingprotein for Xklp2 Q13595 TRA2A Transformer-2 protein homolog alphaP62995 TRA2B Transformer-2 protein homolog beta Q9H4I3 TRABD TraBdomain-containing protein Q15629 TRAM1 Translocating chain-associatedmembrane protein 1 Q12931 TRAP1 Heat shock protein 75 kDa, mitochondrialQ13263 TRIM28 Transcription intermediary factor 1-beta Q9UPN9 TRIM33 E3ubiquitin-protein ligase TRIM33 Q14669 TRIP12 E3 ubiquitin-proteinligase TRIP12 Q15645 TRIP13 Pachytene checkpoint protein 2 homologQ7L0Y3 TRMT10C Mitochondrial ribonuclease P protein 1 Q7Z4G4 TRMT11 tRNA(guanine(10)-N2)- methyltransferase homolog Q7Z2T5 TRMT1L TRMT1-likeprotein Q8IZ69 TRMT2A tRNA (uracil-5-)- methyltransferase homolog AP10155 TROVE2 60 kDa SS-A/Ro ribonucleoprotein P43897 TSFM Elongationfactor Ts, mitochondrial Q99816 TSG101 Tumor susceptibility gene 101protein Q15631 TSN Translin Q99598 TSNAX Translin-associated protein XO43657 TSPAN6 Tetraspanin-6 Q2NL82 TSR1 Pre-rRNA-processing protein TSR1homolog Q99614 TTC1 Tetratricopeptide repeat protein 1 Q6DKK2 TTC19Tetratricopeptide repeat protein 19, mitochondrial Q6P3X3 TTC27Tetratricopeptide repeat protein 27 Q6PGP7 TTC37 Tetratricopeptiderepeat protein 37 Q5R3I4 TTC38 Tetratricopeptide repeat protein 38O95801 TTC4 Tetratricopeptide repeat protein 4 Q14166 TTLL12Tubulin-tyrosine ligase-like protein 12 Q9C0H2 TTYH3 Protein tweetyhomolog 3 Q71U36 TUBA1A Tubulin alpha-1A chain P68363 TUBA1B Tubulinalpha-1B chain Q9BQE3 TUBA1C Tubulin alpha-1C chain Q13748 TUBA3CTubulin alpha-3C/D chain P68366 TUBA4A Tubulin alpha-4A chain Q9NY65TUBA8 Tubulin alpha-8 chain P07437 TUBB Tubulin beta chain Q9H4B7 TUBB1Tubulin beta-1 chain Q13885 TUBB2A Tubulin beta-2A chain Q9BVA1 TUBB2BTubulin beta-2B chain Q13509 TUBB3 Tubulin beta-3 chain P04350 TUBB4ATubulin beta-4A chain P68371 TUBB4B Tubulin beta-4B chain Q9BUF5 TUBB6Tubulin beta-6 chain Q3ZCM7 TUBB8 Tubulin beta-8 chain P23258 TUBG1Tubulin gamma-1 chain Q9BSJ2 TUBGCP2 Gamma-tubulin complex component 2P49411 TUFM Elongation factor Tu, mitochondrial Q6IBS0 TWF2 Twinfilin-2P40222 TXLNA Alpha-taxilin P10599 TXN Thioredoxin Q99757 TXN2Thioredoxin, mitochondrial O95881 TXNDC12 Thioredoxin domain- containingprotein 12 Q9BRA2 TXNDC17 Thioredoxin domain- containing protein 17Q8NBS9 TXNDC5 Thioredoxin domain- containing protein 5 O43396 TXNL1Thioredoxin-like protein 1 Q16881 TXNRD1 Thioredoxin reductase 1,cytoplasmic P04818 TYMS Thymidylate synthase Q2T9J0 TYSND1 Peroxisomalleader peptide- processing protease Q01081 U2AF1 Splicing factor U2AF 35kDa subunit P26368 U2AF2 Splicing factor U2AF 65 kDa subunit O15042U2SURP U2 snRNP-associated SURP motif-containing protein P22314 UBA1Ubiquitin-like modifier-activating enzyme 1 Q9UBT2 UBA2 SUMO-activatingenzyme subunit 2 P62987 UBA52 Ubiquitin-60S ribosomal protein L40 A0AVT1UBA6 Ubiquitin-like modifier-activating enzyme 6 Q9BSL1 UBAC1Ubiquitin-associated domain- containing protein 1 Q5T6F2 UBAP2Ubiquitin-associated protein 2 Q14157 UBAP2L Ubiquitin-associatedprotein 2- like J3QRK5 UBBP4 Protein UBBP4 P63279 UBE2I SUMO-conjugatingenzyme UBC9 P68036 UBE2L3 Ubiquitin-conjugating enzyme E2 L3 P61081UBE2M NEDD8-conjugating enzyme Ubc12 P61088 UBE2N Ubiquitin-conjugatingenzyme E2 N Q9C0C9 UBE2O Ubiquitin-conjugating enzyme E2 O Q7Z7E8 UBE2Q1Ubiquitin-conjugating enzyme E2 Q1 Q15386 UBE3C Ubiquitin-protein ligaseE3C Q9UMX0 UBQLN1 Ubiquilin-1 Q9UHD9 UBQLN2 Ubiquilin-2 Q9NRR5 UBQLN4Ubiquilin-4 P17480 UBTF Nucleolar transcription factor 1 Q04323 UBXN1UBX domain-containing protein 1 P09936 UCHL1 Ubiquitin carboxyl-terminalhydrolase isozyme L1 P15374 UCHL3 Ubiquitin carboxyl-terminal hydrolaseisozyme L3 Q9Y5K5 UCHL5 Ubiquitin carboxyl-terminal hydrolase isozyme L5O94874 UFL1 E3 UFM1-protein ligase 1 Q16739 UGCG Ceramideglucosyltransferase Q9NYU2 UGGT1 UDP-glucose:glycoproteinglucosyltransferase 1 Q6BDS2 UHRF1BP1 UHRF1-binding protein 1 Q13432UNC119 Protein unc-119 homolog A A6NIH7 UNC119B Protein unc-119 homologB Q70J99 UNC13D Protein unc-13 homolog D Q9H3U1 UNC45A Protein unc-45homolog A A4D2Q0 UNC84A SUN domain-containing protein 1 E9PBQ3Uncharacterized protein H3BQZ7 Uncharacterized protein H7C417Uncharacterized protein H7C455 Uncharacterized protein H7C469Uncharacterized protein I3L2F9 Uncharacterized protein Q92900 UPF1Regulator of nonsense transcripts 1 Q9BZI7 UPF3B Regulator of nonsensetranscripts 3B Q9NVA1 UQCC Ubiquinol-cytochrome c reductase complexchaperone P31930 UQCRC1 Cytochrome b-c1 complex subunit 1, mitochondrialP22695 UQCRC2 Cytochrome b-c1 complex subunit 2, mitochondrial P47985UQCRFS1 Cytochrome b-c1 complex subunit Rieske, mitochondr O14949 UQCRQCytochrome b-cl complex subunit 8 Q14694 USP10 Ubiquitincarboxyl-terminal hydrolase 10 P51784 USP11 Ubiquitin carboxyl-terminalhydrolase 11 P54578 USP14 Ubiquitin carboxyl-terminal hydrolase 14Q9Y4E8 USP15 Ubiquitin carboxyl-terminal hydrolase 15 Q53GS9 USP39U4/U6.U5 tri-snRNP-associated protein 2 Q96K76 USP47 Ubiquitincarboxyl-terminal hydrolase 47 Q86UV5 USP48 Ubiquitin carboxyl-terminalhydrolase 48 P45974 USP5 Ubiquitin carboxyl-terminal hydrolase 5 Q93009USP7 Ubiquitin carboxyl-terminal hydrolase 7 Q9NQZ2 UTP3 Something aboutsilencing protein 10 Q9NYH9 UTP6 U3 small nucleolar RNA- associatedprotein 6 homolo P51809 VAMP7 Vesicle-associated membrane protein 7Q9P0L0 VAPA Vesicle-associated membrane protein-associated pro O95292VAPB Vesicle-associated membrane protein-associated pro P26640 VARSValine-tRNA ligase Q99536 VAT1 Synaptic vesicle membrane protein VAT-1homolog P61758 VBP1 Prefoldin subunit 3 P18206 VCL Vinculin P55072 VCPTransitional endoplasmic reticulum ATPase Q96JH7 VCPIP1 Deubiquitinatingprotein VCIP135 P21796 VDAC1 Voltage-dependent anion- selective channelprotein P45880 VDAC2 Voltage-dependent anion- selective channel proteinQ9Y277 VDAC3 Voltage-dependent anion- selective channel protein P08670VIM Vimentin Q96GC9 VMP1 Vacuole membrane protein 1 Q96RL7 VPS13AVacuolar protein sorting- associated protein 13A Q9P253 VPS18 Vacuolarprotein sorting- associated protein 18 hom Q96AX1 VPS33A Vacuolarprotein sorting- associated protein 33A Q96QK1 VPS35 Vacuolar proteinsorting- associated protein 35 Q9UN37 VPS4A Vacuolar protein sorting-associated protein 4A O75351 VPS4B Vacuolar protein sorting- associatedprotein 4B Q9UID3 VPS51 Vacuolar protein sorting- associated protein 51hom Q99986 VRK1 Serine/threonine-protein kinase VRK1 Q7Z5K2 WAPAL Wingsapart-like protein homolog P23381 WARS Tryptophan--tRNA ligase,cytoplasmic Q969T9 WBP2 WW domain-binding protein 2 O75083 WDR1 WDrepeat-containing protein 1 Q9UNX4 WDR3 WD repeat-containing protein 3Q8NI36 WDR36 WD repeat-containing protein 36 Q15061 WDR43 WDrepeat-containing protein 43 Q9NNW5 WDR6 WD repeat-containing protein 6Q9GZS3 WDR61 WD repeat-containing protein 61 Q9BQA1 WDR77 Methylosomeprotein 50 Q6UXN9 WDR82 WD repeat-containing protein 82 O96028 WHSC1Probable histone-lysine N- methyltransferase NSD2 Q5T9L3 WLS Proteinwntless homolog Q9NQW7 XPNPEP1 Xaa-Pro aminopeptidase 1 Q9NQH7 XPNPEP3Probable Xaa-Pro aminopeptidase 3 O14980 XPO1 Exportin-1 Q9HAV4 XPO5Exportin-5 Q96QU8 XPO6 Exportin-6 O43592 XPOT Exportin-T P13010 XRCC5X-ray repair cross- complementing protein 5 P12956 XRCC6 X-ray repaircross- complementing protein 6 Q9H0D6 XRN2 5-3 exoribonuclease 2 P54577YARS Tyrosine--tRNA ligase, cytoplasmic P67809 YBX1 Nuclease-sensitiveelement- binding protein 1 P07947 YES1 Tyrosine-protein kinase YesO95070 YIF1A Protein YIF1A Q5BJH7 YIF1B Protein YIF1B P49750 YLPM1 YLPmotif-containing protein 1 Q96TA2 YME1L1 ATP-dependent zincmetalloprotease YME1L1 Q96MU7 YTHDC1 YTH domain-containing protein 1Q9Y5A9 YTHDF2 YTH domain family protein 2 P31946 YWHAB 14-3-3 proteinbeta/alpha P62258 YWHAE 14-3-3 protein epsilon P61981 YWHAG 14-3-3protein gamma Q04917 YWHAH 14-3-3 protein eta P27348 YWHAQ 14-3-3protein theta P63104 YWHAZ 14-3-3 protein zeta/delta Q8N4Q0 ZADH2Zinc-binding alcohol dehydrogenase domain-containi Q8WU90 ZC3H15 Zincfinger CCCH domain- containing protein 15 Q7Z2W4 ZC3HAV1 Zinc fingerCCCH-type antiviral protein 1 Q9NUD5 ZCCHC3 Zinc finger CCHC domain-containing protein 3 Q6NZY4 ZCCHC8 Zinc finger CCHC domain- containingprotein 8 Q96KR1 ZFR Zinc finger RNA-binding protein O75844 ZMPSTE24CAAX prenyl protease 1 homolog P17028 ZNF24 Zinc finger protein 24O75312 ZNF259 Zinc finger protein ZPR1 Q5BKZ1 ZNF326 DBIRD complexsubunit ZNF326 Q96F45 ZNF503 Zinc finger protein 503 Q86UK7 ZNF598 Zincfinger protein 598 Q15942 ZYX Zyxin

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A small molecule ligand having a structurerepresented by Formula (I):

wherein R is

and wherein the wavy lines

indicate linkage to the carbonyl group of the structure of Formula (I).2. A small molecule ligand which binds to a ligand binding site ofCathepsin B (CTSB), the small molecule ligand is, selected from thegroup consisting of


3. The small molecule ligand of claim 2, wherein the ligand binding siteis defined by the following residues: GQDHCGIESEVVAGIPR of the CTSBprotein having the UniProtKB accession number P07858.